Non-A, non-B hepatitis virus genomic cDNA and antigen polypeptide

BACKGROUND OF THE INVENTION
Field of the Invention
The present invention relates to a non-A, non-B hepatitis virus genomic cDNA and a non-A, non-B hepatitis virus genomic cDNA an a non-A, non-B hepatitis virus antigen polypeptide. More particularly, the present invention is concerned with a non-A, non-B hepatitis virus genomic cDNA which is useful for producing a non-A, non-B hepatitis virus antigen polypeptide and with a non-A, non-B hepatitis antigen polypeptide which is an expression product thereof. The non-A, non-B hepatitis virus genomic cDNA of the present invention is also useful for genetically diagnosing non-A, non-B hepatitis. Further, the non-A, non-B hepatitis antigen polypeptide of the present invention is useful for producing a vaccine for non-A, non-B hepatitis, an immunoglobulin, a polyclonal or monoclonal antibody, an immunological diagnostic reagent, an agent for screening blood for transfusion and an agent for use in affinity chromatography for removing non-A, non-B hepatitis virus from blood for transfusion.
Discussion of Related Art
Definition of non-A, non-B hepatitis virus
The viral hepatitis is a liver disease caused by the infection of a hepatitis virus. Heretofore, hepatitis A virus, hepatitis B virus and hepatitis D (delta) virus have been isolated and identified. The hepatitis D virus (delta-hepatitis virus) is a deficient virus which cannot multiply by itself and requires for its multiplication the co-presence of hepatitis B virus as a helper virus. Therefore, the hepatitis D virus is present only in a patient having hepatitis B. In 1974, it was reported that there were many patients having hepatitis caused by a factor other than the infection with either hepatitis A virus or hepatitis B virus. Such a hepatitis was named "non-A, non-B hepatitis", and researches on the non-A, non-B hepatitis virus have been made extensively and intensively throughout the world. Heretofore, it has been found that a plurality of types of non-A, non-B hepatitis viruses exist. Results of the researches up to now show that the non-A, non-B hepatitis virus is classified into two types according to the infection route, that is, an epidemic hepatitis virus, namely an enterically-transmitted non-A, non-B hepatitis virus, which is spread through blood by transfusion, etc. Of the non-A, non-B hepatitis viruses, only an enterically-transmitted non-A, non-B hepatitis virus which spreads over the areas of Africa, India and Southeast Asia has been virologically identified, but the blood-transmitted non-A, non-B hepatitis virus has not yet been identified.
Hereinbelow, the blood-transmitted non-A, non-B hepatitis is often referred to simply as "NANB hepatitis", and the blood-transmitted non-A, non-B hepatitis virus is often referred to simply as "NANBV". Current situation of the studies on NANB hepatitis and problems.
With respect to the epidemiology, clinical examination, diagnosis, treatment and prevention of the NANB hepatitis, virological studies have been made in the world by the comparison of NANBV with the other hepatitis viruses, based on the knowledge of diagnostics, histopathology, immunology, molecular biology and the like ["Japan Medical Journal", No. 3320, pp. 3-10 1987; "Igaku-no Ayumi (Progress of medicine)", 151(13) pp. 735-923, 1989; "Kan Tan Sui (Liver, Gallbladder, Pancreas)", 21(1) pp. 5-113, 1990; "Jikken Igaku (Experimental Medicine)", 8(3), pp. 201-233, 1990 ]. With respect to the NANB hepatitis, the following findings have been reported.
(1) Epidemiology: In Japan, according to the estimation by the Ministry of Health and Welfare, about 60% of chronic hepatitis patients (namely about 720 thousand patients), about 40% of hepatocirrhosis patients (namely about 100 thousand patients) and about 40% of liver cancer patients (namely about 7 thousand patients) are patients having NANB hepatitis. Further, the mortality attributed to the above-described NANB hepatitis reaches 16 thousand per year. In U.S.A., the number of post-transfusion hepatitis patients reaches 150 to 300 thousand per year and 90% of the post-transfusion hepatitis patients are patients having NANB hepatitis. Further, it is considered that 1 to 6% of the blood donors are NANBV carriers. Further, it is estimated that in the other countries also, the incidence of NANB hepatitis and the ratio of the NANBV carrier are equal to or higher than those in U.S.A. and Japan. Therefore, prevention, early diagnosis and early treatment of the NANB hepatitis are of global importance.
(2) Virology: The NANBV heretofore reported comprises an envelope and assumes a viral particle having a spherical shape of about 50 nm in diameter. The taxonomic observations suggest that the known NANBV is a virus similar to a togavirus or a flavivirus, or a virus of new type different from the togavirus or flavivirus. Further, the results of pathological observations of the cytoplasm of hepatocytes of a plurality of chimpanzees injected with serum of a patient having NANBV hepatitis show that the formation of a tubular structure occurs in the cytoplasm of a hepatocyte of some of the chimpanzees, but does not occur in the cytoplasm of a hepatocyte of the other chimpanzees, and that an intranuclear particle is formed in the cytoplasm of a hepatocyte of some of the chimpanzees. These results and the results of the epidemiological observations, tests on the presence or absence of the chloroform sensitivity and immunological diagnosis suggest that a plurality of types of NANBV-sexist (see, for example, "Science", Vol. 205, pp. 197-200, 1979, "Journal of Infectious Disease", Vol. 148, pp. 254-265, 1983 and "Biseibutsu"(Microorganism), Vol. 5, No. 5, pp. 463-475, 1989). The amount of the NANBV present in the blood of a patient having NANB hepatitis is extremely small as compared to either the amount of a hepatitis A virus present in the feces of a patient having hepatitis A or the amount of a hepatitis B virus present in the blood of a patient having hepatitis B. For example, the amount of hepatitis B virus in the blood of the patient is 10.sup.8 to 10.sup.9 per ml in terms of Chimpanzee Infectious dose (CID), whereas the amount of NANBV in the blood of the patient is only 10.sup.4 to 10.sup.5 per ml in terms of CID (Bradley, D. W.: Research perspective in post-transfusion non-A, non-B hepatitis, in "Infection, Immunity and Blood Transfusion", edited by Dodd, R. Y. & Barker, L. F., published by Alan R. Liss, Inc., New York (1985) pp. 81-97). Further it is known that except for human, there are no animals except chimpanzee that are sensitive to NANBV and that in the cytoplasm of the hepatocyte, a typical tubular structure is occasionally formed by NANBV infection. Since only chimpanzee can be used as an animal for experiment of the NANBV infection, a large number of chimpanzees are required to be used for the study of NANBV. However, the chimpanzee is not easily available and expensive. Therefore, the study of NANBV, identification of NANBV and search for a useful marker for NANBV, is necessarily restricted and delay. In order to solve these problems, various attempts have been made for the study of NANBV. For example, in an attempt, an NANBV genomic cDNA [(referred to as "hepatitis C virus (HCV)"] was cloned from blood plasma of chimpanzees suffering from NANB hepatitis (Science, Vol. 244, pp. 359-362, 1989), and it was confirmed that the antigen (referred to as "C-100") obtained by expressing the cDNA exhibited an antigen-antibody reaction with the antibody in the blood of an NANB hepatitis patient (Science, Vol. 244, pp. 362-364, 1989). Further, in another attempt, a chimpanzee was not used and an NANBV genomic cDNA was cloned from the blood plasma of NANB hepatitis patients, and it was confirmed that the antigen obtained by expressing the cDNA exhibited an antigen-antibody reaction with the antibody in the serum of an NANB hepatitis patient (Gastroenteriologia Japonica, Vol. 24 pp. 540-544 and pp. 545-548, 1989).
(3) Clinical observations: Hepatitis is generally classified either into epidemic hepatitis and sporadic hepatitis according to the number and frequency of the occurrences of hepatitis, or into acute hepatitis, fulminant hepatitis, subacute hepatitis, persistent hepatitis and chronic hepatitis according to the severeness and stage of the hepatitis patients. The latent period of the NANB hepatitis is 2 to 26 weeks. The symptom of NANB hepatitis in the early stage is mild as compared to that of hepatitis B. For example, a patient having NANB hepatitis only becomes feverish and complains of languor. Further, 70% of the patients have anicteric symptom. Therefore, the NANB hepatitis is frequently overlooked. However, the NANB hepatitis is very dangerous because the NANB hepatitis is likely to become chronic and, then, to progress to liver cirrhosis. Illustratively state, 40 to 50% of the patients having NANB hepatitis whose serum exhibits an increased aminotransferase activity develop chronic hepatitis. 10 to 20% of the cases of chronic hepatitis suffer from liver cirrhosis. Further, 0.5 to 1% of blood recipients per year becomes liver cirrhosis patients without subjective symptoms. More seriously, the liver cirrhosis may further progress to liver cancer or hepatoma. Therefore, for preventing biohazard caused by blood transfusion and bleeding, eradication of the NANB hepatitis is a matter of global importance from the viewpoint of public health.
(4) Diagnosis: As mentioned above, the NANBV (blood-transmitted type) has not yet been identified and a viral marker, such as an NANBV antigen, which is useful for the diagnosis of NANB hepatitis has not been known. Therefore, diagnosis of NANB hepatitis has been conducted by examining the titer of the antibody in serum of a patient, which is specific for each of the known pathogenic viruses, such as hepatitis A virus, hepatitis B virus, cytomegalovirus, EB virus, varicella virus and herpes simplex virus, and diagnosing the patient whose serum is negative with respect to the antibody specific for any of the above-mentioned viruses, as having NANB hepatitis, or by performing a histopathological examination through a biopsy of the liver ("Disease of the Liver and biliary system", 8th edition, S. Shenlock, pp. 326-333, 1989, Blackwell Scientific Publications). At the same time, another diagnosis method has also been used. For example, there have been used a method in which the activity of an enzyme in serum, such as GPT [glutamic-pyruvic transaminase, also known as "ALT" (alanine aminotransaminase)], GOT [glutamic-oxalo-acetic transaminase, also known as "AST" (aspartate aminotransferase)], and guanine deaminase (also known as "guanase") is determined ("Kan Tan Sui (Liver, Gallbladder, Pancreas)", Vol. 14, pp. 519-522, 1987). With respect to the GPT or GOT in serum mentioned above, a standard for the diagnosis of NANB hepatitis in which lasting and abnormally high activities of GPT and GOT are utilized as a criterion for the diagnosis of NANB hepatitis, is employed in Japan ("Journal of Blood Transfusion Society in Japan", Vol. 31, No. 4, pp. 316-320, 1985; and "Nippon Rinsho", Vol. 46, p. 2635-2638, 1988). Regarding the immunological diagnosis, in the present situation in which the isolation and identification of NANBV are difficult, an antigen-antibody reaction between an antigen obtained by expression of NANBV and cDNA clone (which has been isolated using the techniques of genetic engineering and the knowledge of immunology) and the serum of an NANB hepatitis patient is used as a criterion. Examples of known antigens include an expression product of an NANBV cDNA prepared from the plasma of an NANB hepatitis patient (European Patent Application Publication No. 363025), an expression product of "HCV" cDNA prepared from the plasma of a chimpanzee having the symptoms of NANB hepatitis (European Patent Application Publication No. 318216 and Japanese Patent Application Laid-Open Specification No. 2-500550) an expression product of an NANBV cDNA derived from the liver of an NANBV-infected chimpanzee (European Patent Application Publication No. 293274, Japanese Patent Publication Specification No. 64-2576 and Japanese Patent Application Laid-Open Specification No. 1-124387). As a method for determining the antigen-antibody reaction, RIA (radioimmunoassay) and EIA (enzyme immunoassay) are generally used. However, these expression products are different in antigenioity. The antigen which is an expression product of HCV cDNA (that is, the C-100 antigen mentioned above) can be some criterion or yardstick for the diagnosis of chronic hepatitis caused by the HCV infection. However, since the region in which the antigen (C-100) exhibits its antigenicity is limited ("Biseibutsu (Microorganism)", Vol. 5, pp. 453-475, 1989; "Kan Tan Sui (Liver, Gallbladder, Pancreas)", Vol. 20, pp. 47-51, 1990; and "Igaku-no Ayumi (Progress of Medicine)", Vol. 151, p. 871, 1989), this antigen is unsatisfactorily from the viewpoint of accurate diagnosis of NANB hepatitis and NANBV infection and from the viewpoint of accurate determination of the progress of a patient suffering from chronic hepatitis and acute hepatitis for treatment thereof. Therefore, it has been desired to obtain a reliable method for the diagnosis and prognosis of the NANB hepatitis.
(5) Therapy and Prevention: Recently, the usefulness of .alpha.- and .beta.- interferons in the treatment of chronic NANB hepatitis have been reported ("Kan Tan Sui (Liver, Gallbladder, Pancreas)" vol. 20, pp. 59-64, 1990; "Igaku-no Ayumi (Progress of Medicine)", vol. 151, pp. 871-876, 1990). However, a suitable does of .alpha.- and .beta.- interferons and a suitable period for administration thereof have not yet been established.
On the other hand, for prevention of NANB hepatitis, various vaccines are used in which the above-mentioned conventional expression products of NANBV cDNAs (European Patent Application Publication No. 363025) or HCV cDNAs (European Patent Application Publication No. 318216) are used as an antigen. However, as is apparent from the fact that the NANBV itself has not yet been isolated and identified before completion of the present invention, it has been impossible to specify an antigen useful for NANBV vaccines from the above-mentioned expression products each having a variety of antigenic determinants (epitopes) and determine the effectiveness and safety of such a specific antigen so that the antigen can be clinically used. Accordingly, there is no NANBV vaccine which can be advantageously put into practical use.
SUMMARY OF THE INVENTION
The present invention have made extensive and intensive studies with a view toward solving the above-mentioned problems by developing a novel NANBV genomic cDNA. As a result, the present invention have surprisingly succeeded in cloning an NANBV genomic cDNA, which not only has excellent reliability as compared to the known NANBV cDNA but also is larger in length than any know NANBV cDNAs and contains the entire region of the open reading frame of the NANBV antigen peptide which can reliably exhibit an antigen-antibody reaction specific for not only sera from patients having chronic NANB hepatitis but also sera from patients having acute NANB hepatitis. This success is attributed to a unique technique of the present inventors such that in order to obtain an authentic NANBV genome, NANBV RNAs are extracted directly from NANBV particles contained in whole blood of a patient having NANB hepatitis or a resected liver of a patient having NANB hepatitis and liver cancer in combination, without multiplying the NANBV in a chimpanzee having unknown factors which are considered to have rendered difficult the isolation of NANBV, although the amount of NANBV in the blood or resected liver is extremely small, that is, as small as about 1/10,000 that of a hepatitis A virus or a hepatitis B virus, but with paying minute care in the operating procedure so that the NANBV and its genome do not undergo cleavage and/or decomposition by the action of body fluids or blood enzymes during the storage of fresh materials for NANBV genome. RNAs thus prepared from fresh human materials are then converted to double-stranded cDNA by means of a reverse transcriptase to obtain a cDNA library. In order to screen an NANBV genome from the cDNA library, the cDNAs are individually inserted in lambda gtll phage vectors and then expressed on the phage plaques at high concentration, followed by screening of NANBV genomic cDNAs by repeatedly conducting enzyme immunoassay (EIA) in which both serum from a convalescent patient having acute NANB hepatitis and serum from a patient having chronic NANB hepatitis are used. Thus, safe production of the NANBV antigen polypeptide with high purity on a large scale at low cost without biohazard, has for the first time been realized by expressing the cDNA of the present invention by recombinant DNA techniques. Based on the above, the present invention has been completed.
Therefore, it is an object of the present invention to provide an NANB hepatitis virus genomic cDNA.
It is another object of the present invention to provide an NANB hepatitis virus antigen polypeptide which is useful as an active ingredient for a diagnostic reagent and a vaccine for NANB hepatitis.
It is still another object of the present invention to provide a method for producing an NANBV antigen polypeptide.
It is a further object of the present invention to provide a diagnostic reagent for NANB hepatitis.
It is still a further object of the present invention to provide a vaccine for NANB hepatitis.
The foregoing and other objects, features and advantages of the present invention will be appended from the following detailed description, appended claims taken in connection with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS
In the Drawings:
FIG. 1(1) and FIG. 1(2) are diagrams showing the relationships between the cDNA clones of the NANBV gene of the present invention, shown relative to the entire region of the NANBV genome;
FIG. 2(1) through FIG. 2(16) show the nucleotide sequence of the entire region of the NANBV genomic cDNA according to the present invention (SEQ ID NO: 1) and the amino acid sequence (SEQ ID NO: 2) coded for by the nucleotide sequence; and
FIG. 3 is a diagram showing the hydrophobicity profiles of both of the NANBV of the present invention and the Japanese encephalitis virus (JEV), in which the hydrophobicity index of the NANBV is compared with that of the JEV.

DETAILED DESCRIPTION OF THE INVENTION
Essentially, according to the present invention there is provided an isolated deoxyribonucleic acid comprising at least one nucleotide sequence selected from the group consisting of a nucleotide sequence comprising at least part of the non-A, non-B hepatitis virus entire nucleotide sequence (SEQ ID NO: 1) from the 1st to 9416th nucleotides shown in FIG. 2(1) through FIG. 2(16) hereof and a nucleotide sequence complementary to said nucleotide sequence, or comprising at least one nucleotide sequence obtained by substituting at least one nucleotide of said nucleotide sequence in accordance with the degeneracy of the genetic code.
In another aspect of the present invention, there is provided an isolated antigen polypeptide comprising at least one amino acid sequence comprising at least part of an amino acid sequence coded for by a deoxyribonucleic acid comprising a coding region from the 333rd to 9362nd nucleotides of the non-A, non-B hepatitis virus nucleotide sequence (SEQ ID NO: 1) shown in FIG. 2(1) through FIG. 2(16) hereof.
In the present invention, unless otherwise specified, the left end and right end of the sequence of deoxyribonucleotides are the 5' end and 3' end, respectively. Further, unless otherwise specified, the left end and right end of the amino acid sequences of peptides are the N-terminus and C-terminus, respectively.
The NANBV genomic cDNA of the present invention and the NANBV antigen polypeptide as an expression product thereof can be prepared and identified in accordance with the following steps (I) to (VII).
Step (I): Selection and collection of a material for extracting an NANBV RNA.
As a material for extracting the NANBV RNA, there may be used, for example, blood, lymph, ascites and hepatocyte of an NANBV carrier, or of a human or a chimpanzee suffering from NANB hepatitis, and hepatocyte of a patient suffering from NANB hepatitis and liver cancer or hepatoma in combination. Since the materials derived from a chimpanzee may contain NANBV in a relatively small amount as compared to the materials derived from a human and a chimpanzee has unknown factors which are considered to have rendered difficult the isolation of NANBV, the use of the materials derived from a human is preferred. Of blood, lymph, ascites and hepatocytes from a human, blood can most easily be obtained in a large amount. For example, blood which is not acceptable for use as blood transfusion is available from a blood bank in a large amount. Such blood can advantageously be used as a material for extracting an NANBV RNA. When blood is used as a material, blood is separated into plasma and erthrocytes. The thus obtained plasma is examined to determine whether or not the plasma is negative to the surface antigen of hepatitis B virus (WHO expert committee on viral hepatitis: Advances in viral hepatitis, WHO Technical Report Series, 602, 28-33, 1977) and negative to a genomic DNA of hepatitis B virus (Brechot, C., Hadchouel, M., Scotto, J., Degos, F., Charnay, P., Trepo, C., Tiolais, P.: Detection of hepatitis B virus DNA in liver and serum: a direct appraisal of the chronic carrier state. Lancet 2: 765-768, 1981). Further, the plasma is examined with respect to the activities of enzymes, such as GPT (Wroblewski, F. & LaDue, J. S.: Serum glutamic-pyruvic transaminase in cardiac and hepatic disease, Proc. Soc. Exp. Biol. Med., 91, 569, 1956), GOT, guanase and the like, which are employed as the criterion for the diagnosis of NANB hepatitis. The above-mentioned procedures of the separation of blood into plasma and erthrocytes and the examination of the plasma are conducted with respect to blood of different lots. The plasma which is negative to both surface antigen and genomic cDNA of hepatitis B virus and exhibits extremely high activities of the above-mentioned enzymes, for example, a GPT activity of 35 IU/ml of more, is pooled.
The number of the NANB hepatitis virus particles in blood is extremely small as compared to that of the hepatitis B virus particles as mentioned hereinbelow. From the results of the infection experiment, the number of the NANB hepatitis virus particles in blood is estimated to be about 1/10,000 of the number of the hepatitis B virus particles (Bradley, D. W., (1985); Research perspectives in post-transfusion non-A, non-B hepatitis, in "Infection, Immunity and Blood Transfusion", edited by Dodd, R. Y. & Barker, L. F., published by Alan R. Liss, Inc., New York, pp. 81-97). Therefore, for the extraction of the RNA, it is preferred to use blood in a large amount, for example, in an amount as large as about 3 to 10 liters. Fresh whole blood to be used as a material for extracting and NANB RNA from NANBV particles is stored at 1 to 5.degree. C. in order to prevent NANBV and its gene from being denatured and to prevent its gene from being cleaved or decomposed by the action of an enzyme. It is also desirable to complete the preparation of NANBV RNAs by Step (II) within 48 to 72 hours from the collection of the fresh whole blood. When a hepatocyte is used as a material, about 1 to 3 g of a non-cancerous or a cancerous portion of a liver tissue resected from a patient having hepatoma or liver cancer which is a complication of a chronic NANB hepatitis may advantageously be used. Hepatocyte to be used as a material is stored in a frozen state at -70.degree. C.
Step (II): Preparation of the NANBV RNA
From the material obtained in Step (I), the RNA may be extracted and purified by conventional methods. For example, when fresh whole blood is used as the material, about 2 to 10 liters of fresh whole blood is subjected to low-speed centrifugation to collect a plasma fraction as a supernatant. The virus fraction is obtained from the plasma through purification for use in the subsequent procedure for the extraction and purification of the RNA.
On the other hand, when hepatocyte is used as a material for extracting the NANBV RNA, about 5 to 30-fold volume of a diluent containing ribonuclease inhibitor is added to the liver tissue. Then, according to the conventional method using a homogenizer and the like, the liver tissue is crushed or disrupted to obtain a homogenate of hepatocyte. As a diluent, 10 to 150 mM of a conventional buffer may be used. Then, the homogenate is subjected to low-speed centrifugation to collect a supernatant. The collected supernatant is used as a original solution for the extraction and purification of the NANBV RNA. The extraction and purification of the NANBV RNA may be conducted by the conventional method, for example, an extraction method in which a mixture of a ribonuclease inhibitor, such as heparin, diethyl pyrocarbonate and guanidine thiocyanate, with a surfactant, a chelating agent, or a reducing agent capable of enhancing the denaturation of a protein, is used; a method in which fractionation is conducted by density gradient centrifugation using sucrose, cesium chloride, cesium trichloroacetate, Ficoll (Pharmacia Fine Chemicals AB, Sweden) or the like as a solute of a gradient; a method in which separation is conducted by affinity column utilizing the 3'-terminal poly A chain which an mRNA specifically has; a separation method in which an mRNA-bonded poly-some is obtained by the immunoprecipitation using an antibody specific for a protein synthesized on the polysome; a phenol extraction method based on a principle of two-phase separation; a precipitation method by the use of a polyethylene glycol, a dextran sulfate, an alcohol or the like. The above-mentioned methods may be used individually or in combination. The above-mentioned procedure for extracting and purifying the NANBV RNA may preferably be conducted at pH 3 to 10 in order to prevent the irreversible denaturation of the RNA.
Step (III): Preparation of a double-stranded cDNA from the NANBV RNA
Using the above-obtained NANBV RNA as a template, a cDNA may be prepared by a customary method. That is, using an oligodeoxythymidine and a random hexanucleotide primer as primers and using a reverse transcriptase, a cDNA complementary to the NANBV RNA is synthesized using the NANBV RNA as a template to obtain a double-strand comprising the cDNA and the NANBV RNA which are complementarily bonded to each other. Then, the thus obtained double-strand is reacted with ribonu-clease H so that the NANBV RNA is decomposed and removed from the cDNA. Thus, a single-stranded cDNA is obtained. Using the obtained single-stranded cDNA as a template, a double-stranded cDNA is synthesized by means of a DNA synthase. The double-stranded cDNA synthesis may easily be conducted using a commercially available kit for cDNA synthesis, for example, cDNA Synthesis System Plus.RTM. (manufactured and sold by Amersham, England), cDNA System Kit.RTM. (manufactured and sold by Pharmacia LKB, Sweden), cDNA Synthesis Kit.RTM. (manufactured and sold by Boehringer Mannheim GmbH, West Germany), and the like. When the quantity of the synthesized cDNA is small, the cDNA can be amplified using a conventional method, such as PCR (polymerase chain reaction) method ("PCR Technology", edit by H. A. Erlich, published by Stockton Press, 1989) using a PCR kit, such as AmpliTaq (manufactured and sold by Perkin Elmer Cetus, U.S.A.).
Step (IV): Preparation of a cDNA library
Using the cDNA prepared in Step (III), a cDNA library is prepared by a customary method. That is, the cDNA prepared in Step (III) is cut into fragments having different lengths and the resultant various cDNA fragments are individually ligated to replicable cloning vectors, to thereby obtain a cDNA library. As a replicable cloning vector, any known or commercially available vectors, such as phage genes, cosmids, plasmids and animal virus genes may be sued. When a phage gene or a cosmid is used as a replicable vector, in order to attain high stability and high transforming ability of the vector after each of the cDNA fragments has been individually inserted therein, the in vitro packaging of each of the cDNA-inserted vectors is conducted by a customary method. Thus, the cDNA-inserted vectors are obtained in the form of a recombinant phage particle. The obtained phage particles are used as a cDNA library for cDNA cloning. On the ether hand, when a plasmid is used as a replicable vector, the above-mentioned cDNA fragments are individually inserted in the plasmid vectors and the resultant cDNA-inserted vectors are then individually introduced into host cells, such as cells of Escherichia coli, Bacillus subtilis, yeast or the like, according to a customary method. The thus obtained transformants are used as a cDNA library for cDNA cloning. Further, when the animal virus gene is used as a replicable vector, the above-mentioned cDNA fragments are individually inserted in the virus gene vectors and the resultant recombinant viruses are then individually transfected into sensitive animal cells according to a standard method and multiplied in the cells. In the case of the recombinant virus, the obtained recombinant viruses as such are used as a cDNA library.
The preparation of the cDNA library may easily be conducted using a commercially available kit, for example, a cDNA cloning system lambda gt10 and lambda gt11 (manufactured and sold by Amersham, England; BRL Inc., U.S.A.; and Stratagene Inc., U.S.A.), an in vitro packaging system (manufactured and sold by Amersham, England; BRL Inc., U.S.A.; and Stratagene Inc., U.S.A.) and the like.
Step (V): Cloning of a cDNA containing an NANBV gene from the cDNA library
In this step, a cDNA clone containing a NANBV gene is obtained. When the cDNA library is comprised of transformants, the transformants are cultured on a standard agar medium to form colonies. On the other hand, when the cDNA library is comprised of recombinant phage particles or recombinant viruses, these phage particles or recombinant viruses are used to infect known sensitive host cells, such as Escherichia coli, Bacillus subtilis, yeast, animal cell culture and the like, and cultured to form a plaque, or to multiply the infected cells. The above-obtained transformant colonies, plagues or infected cells are subjected to immunoassay by as least one of the standard methods individually using serum from a convalescent patient having acute NANB hepatitis, serum from a patient having chronic NANB hepatitis, and serum from chimpanzee infected with an NANBV irrespective of whether or not the NANBV is of the type which causes a tubular structure to be formed in the cytoplasm of the hepatocyte of the chimpanzee, so that colonies, plaques or infected cells which have produced an NANBV antigen specifically reacted with at least one of the above-mentioned sera are selected and isolated. For the strict selection of the colonies, plaques and infected cells, it is preferred that the above procedure be repeated. From each of the thus selected and isolated colonies, plaques or the infected cells, a cDNA clone containing an NANBV gene is isolated according to a standard method described in T. Maniatis et al., Molecular Cloning, A Laboratory manual, published by Cold Spring Harbor Laboratory, U.S.A., pp. 309-433 (1982). The immunoassay may be conducted by, for example, an enzyme-labeled antibody technique in which an antibody labeled with an enzyme, such as peroxidase and alkaline phosphatase is used; and a fluorescent antibody technique in which an antibody labeled with fluorescein isothiocyanate, europium or the like is used. It is preferred that the immunoassay by the above-mentioned technique be conducted by an indirect method because with the indirect method, high sensitivity immunoassay can be attained even by the use of an extremely small amount of serum from a patient. As a primary antibody to be used in the indirect method, serum from a patient having NANB hepatitis or serum from a chimpanzee having NANB hepatitis may preferably be employed because these sera contain an antibody specific for an NANBV antigen in relatively large amount. As a secondary antibody to be used in the indirect method, a commercially available anti-human Ig (immunoglobulin) antibody labeled with an enzyme, a fluorescent substance or the like may be used.
A specimen to be subjected to immunoassay may be prepared according to a conventional method, for example, a blotting method in which nucleic acids and proteins of the colonies, plaques and infected cells are adsorbed on a filter membrane, a method in which a microplate or a slide glass for microscopy is used, or the like. When the blotting method is used in combination with an indirect, enzyme-labeled antibody technique, the selection of the intended colonies, plaques or infected cells from an extremely large number of the original colonies, original plaques or original infected cells can be conducted easily and promptly. In this case, blotting is conducted by contacting a commercially available filter made of nitrocellulose, cellulose acetate, nylon or the like, with the colonies, plaques or infected cells.
The above-obtained cDNA clone is a part of the NANBV gene. Therefore, in order to obtain cDNA clones covering the entire region of the NANBV gene, it is requisite to extend the cDNA clone by a method in which cDNA fragments adjacent to the cDNA clone are isolated by using 3'- and 5'-terminals of the cDNA clone as a probe. In this case, the technique which is known as "gene walking" (also known as "genomic walking" or "chromosome walking") may be employed ("DNA cloning volume III", edited by D. M. Glover, pp 37-39, IRL Press, 1987; "Molecular Cloning--a laboratory manual" 2nd edit., T. Maniatis et al, 3.21-3.23, 1989). by the repetition of the cloning procedure and the gene walking, the entire region of the NANBV gene can be obtained in the form of cDNA clones.
In this step, it is preferred to determine the nucleotide sequence of each of the obtained cDNA clones. The determination of the nucleotide sequence of the cDNA clone may generally be conducted according to a conventional method, for example, the Maxam-Gilbert method, the dideoxy chain termination method (Analytical Biochemistry, 152, 232-238, 1986), or the like.
Based on the determined nucleotide sequence, the amino acid sequence can be determined. The sequencing of the amino acids is conducted from the location of the initiation codon (ATG on the cDNA or AUG on the mRNA). Important portions of the amino acid sequence, for example, a hydrophilic portion, which is considered to constitute an epitope, can be identified by synthesizing a peptide corresponding to each hydrophillic portion and purifying the synthesized polypeptide by high performance liquid chromatography (HPLC), followed by subjecting the purified peptide to enzyme immunoasssy (EIA) or radioimmunoassay (RIA).
The cDNA clones are preferably classified into groups according to the respective properties of the NANBV antigen polypeptides coded for by the cDNA clones in order to distinguishing clones from one another. In this connection, the location of each cDNA clone on the restriction map of the NANBV gene can be used as a yardstick for the classification [see FIG. 1(1) and FIG. 1(2)]. Further, it has been found that some of NANBVs have the ability to cause a tubular structure to be formed in the cytoplasm of a hepatocyte of a chimpanzee, and some of NANBV do not have such ability (Science, 205, pp. 197-200, 1979). Therefore, the cDNA clones may be identified and classified by examining the serological reactivity of each cDNA clone with serum from a chimpanzee infected with an NANBV of the type which causes a tubular structure to be formed in the cytoplasm of the hepatocyte of the chimpanzee and with serum from a chimpanzee infected with an NANBV of the type which does not cause a tubular structure to be formed in the cytoplasm of the hepacyte of the chimpanzee. The examination of this serological reactivity may be conducted by immunoassay mentioned above.
In the present invention, as shown in FIGS. 1(1) and 1(2), the cDNA clones of the NANBV gene of the present invention are identified with prefix "BK".
FIG. 1(1) is a diagram showing the relationships between the cDNA clones of the NANBV gene of the present invention, shown relative to the entire region of the NANBV gene, and FIG. 1(2) is a diagram showing the relationships between the cDNA clones obtained by gene walking, shown relative to the entire region of the NANBV gene.
These BK NANBV cDNA clones include, for example, Escherichia coli BK 108 (deposited at Fermentation Research Institute, Japan under the accession number FERM BP-2971), Escherichia coli BK 129 (deposited at Fermentation Research Institute, Japan under the accession number FERM BP-2972), Escherichia coli BK 138 (deposited at Fermentation Research Institute, Japan under the accession number FERM BP-2975), and Escherichia coli BK 172 (deposited at Fermentation Research Institute, Japan under accession number FERM BP-2975). Escherichia coli BK 157, Escherichia coli BK 166 (deposited at Fermentation Research Institute, Japan under the accession number FERM BP-2975), and Escherichia coli BK 172 (deposited at Fermentation Research Institute, Japan under accession number FERM BP-2976). These seven BK NANBV cDNA clones are considered to cover at least the entire region of the open reading frame of the NANBV gene and probably the entire region of the NANBV gene.
The nucleotide sequence (SEQ ID NO: 1) of the entire region of the NANBV gene which is covered by the above-mentioned BK NANBV cDNA clones and the amino acid sequence (SEQ ID NO: 2) which is coded for by this nucleotide sequence are shown in FIG. 2(1) through FIG. 2(16). Based on the entire NANBV nucleotide sequence (SEQ ID NO: 1) and the entire NANBV amino acid sequence (SEQ ID NO: 2) shown in FIG. 2(1) through FIG. 2(16), various studies and observations can be made with respect to the homology of the nucleotide sequence and amino acid sequence of the NANBV gene to those of other virus genes, the hydrophobicity index (hydrophobicity/hydrophilicity profile), the structure of the NANBV gene, the regions of epitopes (antigenic determinants) and the like.
With respect to the homology, studies can be made by comparison of the nucleotide sequence and amino acid sequence of the NANBV gene with those of various viruses whose gene are well known (Japanese Patent Application Laid-Open specification No. 62-286930 and "Virology", Vol. 161, pp. 497-510, 1987) and those of other viruses, such as bovine virus diarrhea-mucosal disease virus ("Virology", Vol. 165, pp. 497-510, 1988), swine cholera virus ("Virology", Vol. 171, pp. 555-567, 1989), tobacco vein mottling virus ("Nucleic Acid Research, Vol. 165, pp. 5417-5430, 1986), etc.
With respect to the analysis of the hydrophobicity index, studies can be made by techniques using, for example, a genetic information processing software, SDC-Genetyx (manufactured and sold by SDC Software Co., Ltd., Japan), Doolittle's program (Journal of Molecular Biology, Vol. 157, pp. 105-132, 1982) and the like.
FIG. 3 is a diagram showing the hydrophobic profiles of both of the NANBV of the present invention and the Japanese encephalitis virus (JEV), in which the respective hydrophobic indexes of both viruses are compared with each other. A significant similarity is found between the gene structure of the NANBV gene and that of the JEV gene. As shown in FIG. 3, the polypeptide of the NANBV of the present invention contains three structural proteins, namely, core protein (C), pre-matrix protein (PreM) that is further processes to matrix protein (M) and envelope protein (E), and seven nonstructural proteins, NS1, NS2a, NS2b, NS3, NS4a, NS4b and NS5. These proteins are, respectively, coded for by the following nucleotide sequences.
C protein: from the 333rd to 677th nucleotides
M protein: from the 678th to 905th nucleotides
E protein: from the 906th to 1499th nucleotides
NS1 protein: from the 1500th to 2519th nucleotides
NS2 protein: from the 2520th to 3350th nucleotides
NS3 protein: from the 3351st to 5177th nucleotides
NS4a protein: from the 5178th to 5918th nucleotides
NS4b protein: from the 5919th to 6371th nucleotides
NS5 protein: from the 6372nd to 9362nd nucleotides
These nucleotide sequences are useful for the diagnosis of NANB hepatitis. Polypeptides respectively coded for by these nucleotide sequences are useful as antigens for not only vaccines but also diagnostic reagents for NANB hepatitis.
The above-mentioned three structural proteins are represented by the 1st(MET) to 389th(Gly) amino acids of SEQ ID NO: 2 shown in FIG. 2(1) through FIG. 2(3). The 1st methionine residue is the residue that is coded for by the initiation codon.
By further studies by the present inventors, it has been found that the following nucleotide sequences contain epitopes which are reactive to an anti-NANBV antibody:
nucleotide sequences respectively of the 333rd to 422nd nucleotides, of the 333rd to 1499th nucleotides, of the 333rd to 6371st nucleotides, of the 474th to 563rd nucleotides, of the 906th to 953rd nucleotides, of the 1020th to 1046th nucleotides, of the 1020th to 1121st nucleotides, of the 1194th to 1232nd nucleotides, of the 1209th to 1322nd nucleotides, of the 4485th to 4574th nucleotides and of the 5544th to 5633rd nucleotides of SEQ ID NO: 1.
As described hereinbelow, the above-mentioned nucleotide sequences or nucleotide sequences containing such nucleotide sequences as part of the whole sequences, can be effectively used not only for producing NANBV antigen polypeptides by recombinant DNA technique or chemical synthesis but also for diagnosing NANB hepatitis by hybridization or polymerase chain reaction (PCR).
Further, it has been found that a first nucleotide sequence comprising at least six nucleotides of the entire region from the 1st to 9416th nucleotides of SEQ ID NO: 1 shown in FIG. 2(1) through FIG. 2(16) is useful as a probe for hybridization or as a primer for polymerase chain reaction in the diagnosis of NANB hepatitis and that a polypeptide comprising at least four amino acids, which is coded for by a nucleotide sequence of at least twelve nucleotides of SEQ ID NO: 1 of the nucleotide sequence of the 333rd to 9362nd nucleotides of SEQ ID NO: 1 is effective as an antigen not only for a vaccine but also for a diagnostic reagent for NANB hepatitis. Further, as is well known in the art, a second nucleotide sequence complementary to the first nucleotide sequence is also useful as a probe for hybridization or as a primer for polymerase chain reaction in the diagnosis of NANB hepatitis. Further, a nucleotide sequence obtained by substituting at least one nucleotide of at least part of the coding region of the first nucleotide sequence of the NANBV in accordance with the degeneracy of the genetic code can also be used for producing the antigen polypeptide of the present invention by recombinant DNA technique.
Accordingly, the isolated deoxyribonucleic acid of the present invention comprises at least one nucleotide sequence selected from the group consisting of a first nucleotide sequence comprising at least part of the non-A, non-B hepatitis virus entire nucleotide sequence from the 1st to 9416th nucleotides of SEQ ID NO: 1 shown in FIG. 2(1) through FIG. 2(16) hereof and a second nucleotide sequence complementary to the first nucleotide sequence, or comprises at least one nucleotide sequence obtained by substituting at least one nucleotide of the first nucleotide sequence in accordance with the degeneracy of the genetic code.
In one preferred embodiment of the present invention with respect to the deoxyribonucleic acid, the first nucleotide sequence comprises at least six nucleotides of the non-A, non-B hepatitis virus entire nucleotide sequence from the 1st to 9416th nucleotides of SEQ ID NO: 1 shown in FIG. 2(1) through FIG. 2(16) hereof.
In another preferred embodiment of the present invention with respect to the deoxyribonucleic acid, the first nucleotide sequence comprises at least one nucleotide sequence selected from the group consisting of a nucleotide sequence of the 333rd to 422nd nucleotides, a nucleotide sequence of the 333rd to 677th nucleotides a nucleotide sequence of the 333rd to 1499th nucleotides, a nucleotide sequence of the 333rd to 6371st nucleotides, a nucleotide sequence of the 474th to 563rd nucleotides, a nucleotide sequence of the 678th to 905th nucleotides, a nucleotide sequence of 906th to 953rd nucleotides, a nucleotide sequence of the 906th to 1499th nucleotides, a nucleotide sequence of the 1020th to 1046th nucleotides, a nucleotide sequence of the 1020th to 1121st nucleotides, a nucleotide sequence of the 1194th to 1232nd nucleotides, a nucleotide sequence of the 1209th to 1322nd nucleotides, a nucleotide sequence of the 1500th to 2519th nucleotides, a nucleotide sequence of the 2520th to 3350th nucleotides, a nucleotide sequence of the 3351st to 5177th nucleotides, a nucleotide sequence of the 4485th to 4574the nucleotides, a nucleotide sequence of the 5178th to 5918th nucleotides, a nucleotide sequence of the 5544th to 5633rd nucleotides, a nucleotide sequence of the 5919th to 6371st nucleotides, a nucleotide sequence of the 6372nd to 9362nd nucleotides and a nucleotide sequence from the 1st to 9416th nucleotides of SEQ ID NO: 1.
The isolated antigen polypeptide of the present invention comprise at least one amino acid sequence comprising at least part of an amino acid sequence coded for by a deoxyribonucleic acid comprising a coding region from the 333rd to 9362nd nucleotides of the non-A, non-B hepatitis virus nucleotide sequence (SEQ ID NO: 1) shown in FIG. 2(1) through FIG. 2(16) hereof.
In one preferred embodiment of the present invention with respect to the antigen polypeptide, the antigen polypeptide comprises at least one amino acid sequence of at least four amino acids, which is coded for by a nucleotide sequence of at least twelve nucleotides of the nucleotide sequence of the 333rd to 9362nd nucleotides of SEQ ID NO: 1.
In another preferred embodiment of the present invention with respect to the antigen polypeptide, the antigen polypeptide comprises an amino acid sequence code for by a nucleotide sequence selected form the group consisting of a nucleotide sequence of the 333rd to 422nd nucleotides, a nucleotide sequence of the 333rd to 677th nucleotides, a nucleotide sequence of the 333rd to 1499th nucleotides, a nucleotide sequence of the 333rd to 6371st nucleotides, a nucleotide sequence of the 474th to 563rd nucleotides, a nucleotide sequence of the 678th to 905th nucleotides, a nucleotide sequence of the 906th to 953rd nucleotides, a nucleotide sequence of the 906th to 1499th nucleotides, a nucleotide sequence of the 1020th to 1046th nucleotides, a nucleotide sequence of the 1020th to 1121st nucleotides, a nucleotide sequence of the 1194th to 1232nd nucleotides, a nucleotide sequence of the 1209th to 1322nd nucleotides, a nucleotide sequence of the 1500th to 2519th nucleotides, a nucleotide sequence of the 2520th to 3350th nucleotides, a nucleotide sequence of the 3351st to 5177th nucleotides, a nucleotide sequence of the 4485th to 4574th nucleotides, a nucleotide sequence of the 5178th to 5918th nucleotides, a nucleotide sequence of the 5544th to 5633rd nucleotides, a nucleotide sequence of the 5919th to 6371st nucleotides, a nucleotide sequence of the 6372nd to 9362nd nucleotides and a nucleotide sequence of the 333rd to 9362nd nucleotides of SEQ ID NO: 1.
Furthermore, it should be noted that since a polypeptide coded for by the entire coding region of the NANBV (SEQ ID NO: 1) shown in FIG. 2(1) through FIG. 2(16), such a polypeptide has a broad antigen-antibody reaction spectrum and therefore can react to a wide variety of antibodies produced by infection with NANB hepatitis virus as compared to an antigen containing a single epitope, so that it has high sensitivity in detecting NANB hepatitis.
Step (VI): Expression of the NANBV genomic cDNA clone and a mass production of an NANBV antigen polypeptide.
In order to express the cloned cDNA of an NANBV antigen gene to produce an NANBV antigen polypeptide on a commercial scale, part or whole of the cloned cDNA present in the cDNA clone in taken out from the replicable cloning vector and recombined with a replicable expression vector. Illustratively stated, part or whole of the cDNA of each cDNA clone is cut off using a restriction enzyme to obtain a DNA fragment containing an NANBV antigen gene (hereafter referred to as "NANBV DNA fragment"). The NANBV DNA fragment is then inserted in a replicable expression vector by a customary method. When one DNA fragment is inserted in an expression vector, one type of antigen polypeptide can be produced by gene expression. When two or more of different DNA fragments are inserted in sequence in an expression vector, an antigen polypeptide can be produced by gene expression in the form of a fused polypeptide comprising polypeptides coded for the inserted DNA fragments.
As the replicable expression vector which may be used in this step, any conventionally known or commercially available expression vector can be used. Examples of expression vectors include plasmid vector pSN508 for enterobacteria (U.S. Pat. No. 4,703,005), plasmid vector pBH103 for yeast, and its series (Japanese Patent Application Laid-Open Specification No. 63-22098), plasmid pJM105 (Japanese Patent application Laid-Open Specification No. 62-286930), an attenuated chicken pox virus gene (Japanese Patent Application Laid-Open Specification No. 53-41202), an attenuated Marek's disease virus (The Journal of Japanese Society of Veterinary, 27, 20-24 (1974), and Gan Monograph on Cancer Research, 10, 91-107 (1971)), plasmid pTTQ series (manufactured and sold by Amersham, England), plasmid pSLV series (manufactured and sold by Pharmacia LKB, Sweden), and the like.
The NANBV DNA-inserted expression vectors are individually introduced or transfected into host cells sensitive to the vector according to a conventional method, to obtain transformants. Then, from the transformants, the transformant(s) which has produced an NANBV antigen polypeptide or an NANBV particle is selected. The production of an NANBV antigen polypeptide (or an NANBV particle) may be detected by the immunoassay mentioned above in Step (V). When an animal virus gene is used as an expression vector, a recombinant virus having an NANBV antigen polypeptide on the surface thereof may be obtained. Such a recombinant virus may advantageously be used as a raw material for a multifunctional vaccine having not only an antigenicity inherent in the virus vector but also an antigenicity of the NANBV.
By culturing the transformant or recombinant virus obtained above according to a customary method, an NANBV antigen polypeptide can be produced in the culture of the transformant or recombinant virus on a commercial scale. With respect to the details of the method in which an animal virus gene is used as an expression vector, reference may be made to European patent Application Publication No. 0 334 530 A1.
Accordingly, in still another aspect of the present invention, there is provided a method for producing a non-A, non-B hepatitis virus antigen polypeptide, which comprises:
(a) inserting a deoxyribonucleic acid into a replicable expression vector selected from a plasmid and an animal virus gene to obtain a replicable recombinant DNA comprising the plasmid and the deoxyribonucleic acid inserted therein when the replicable expression vector is a plasmid or obtain a recombinant virus comprising the animal virus gene and the deoxyribonucleic acid inserted therein when the expression vector is an animal virus gene,
the deoxyribonucleic acid comprising a nucleotide sequence selected from the group consisting of a first nucleotide sequence comprising at least part of a region from the 1st to 1499th nucleotides or at least part of a region from the 1500th to 9416th nucleotides of the non-A, non-B hepatitis virus entire nucleotide sequence (SEQ ID NO:1) shown in FIG. 2(1) through FIG. 2(16) hereof and a nucleotide sequence obtained by substituting at least one nucleotide of the first nucleotide sequence in accordance with the degeneracy of the genetic code;
(b) transfecting cells of a microorganism or eukaryotic cell culture with the recombinant DNA when the replicable expression vector used in step (a) is a plasmid, to thereby form a transformant, followed by selection of the transformant from parent cells of the microorganism or eukaryotic cell culture;
(c) culturing the transformant obtained in step (b) to thereby express the deoxyribonucleic acid and produce a non-A, non-B hepatitis virus antigen peptide, or culturing the recombinant virus obtained in step (a) to thereby express the deoxyribonucleic acid and the animal virus gene and produce a non-A, non-B hepatitis virus antigen peptide in the form of a multiplied recombinant virus comprising an animal virus and a non-A, non-B hepatitis virus antigen peptide contained on the surface thereof; and
(d) isolating the non-A, non-B hepatitis virus antigen peptide alone or in the form of the multiplied recombinant virus.
Furthermore, by using part or whole of the cDNA of FIG. 2(1) through FIG. 2(16) (SEQ ID NO: 1) as a template, an RNA or mRNA corresponding thereto can be synthesized by in vitro transcription according to a standard method. For example, an RNA or mRNA corresponding to the entire region of the cDNA of FIG. 2(1) through FIG 2(16) (SEQ ID NO:1) can synthesized using as a template the entire region of the cDNA which is prepared by digesting plasmid pDM-18 (constructed in Example 2) with restriction enzyme HindIII, followed by in vitro transcription by means of T7 RNA polymerase and cap analog. The thus synthesized RNA or mRNA covers the entire region of NANBV gene, that is, the RNA or mRNA is substantially naked NANBV genome. Therefore, when the mRNA is transfected into animal cells, an infectious NANBV particle can be obtained. The above-mentioned mRNA can be synthesized by means of, for example, a commercially available mRNA Capping Kit (manufactured and sold by Stratagene, U.S.A.) in a conventional manner. With respect to the details of the operating procedure for the synthesis, reference may be made to "Current Protocols in Molecular Biology", 10.17.1-10.17.5, published by John Wiley & Sons, 1989). The RNA which can be obtained using part or whole of the cDNA of FIG. 2(1) through FIG. 2(16) (SEQ ID NO: 1), is part or whole of the NANBV genome and, therefore, it is useful for studying NANBV and infectious disease caused thereby.
Step (VII): Purification of an NANBV antigen polypeptide
The NANBV antigen polypeptide produced in the culture of the transformant or recombinant virus may be purified using an appropriate combination of customary techniques selected from, for example, salting-out; adsorption and desorption using a silica gel, an activated carbon or the like; precipitation by an organic solvent; fractionation by ultracentrifugation; separation by ion exchange chromatography or affinity column chromatography; fractionation by high-performance liquid chromatography or electrophoresis, and the like.
When the NANBV antigen polypeptide is purified from the culture of an E. coli transformant or a yeast transformant, from the viewpoint of effective removal of allergens derived from E. coli and yeast which cause the quality of the final product of the NANBV antigen polypeptide to be markedly lowered, it is preferred that the purification be conducted by, for example, the steps of (1) adsorption and desorption using a silica gel, removal of impurities by adsorption on an activated carbon and (2) fractionation by density gradient centrifugation in this order (Japanese Patent Application Laid-Open Specification No. (63-297). When the NANBV antigen polypeptide is purified from the culture of a recombinant virus, e.g., the culture of a recombinant virus-infected cells, a high purity NANBV antigen polypeptide can be obtained by subjecting a crude solution containing the antigen to purification by ultracentrifugation and density gradient centrifugation repeatedly.
Thus, a solution containing a purified NANBV antigen polypeptide of the present invention is obtained. If desired, the solution may be lyophilized to obtain a purified NANBV antigen polypeptide in a dry form.
The mixed antigen polypeptide of the present invention may be obtained by mixing at least two different types of the NANBV antigen polypeptides obtained by gene expression of at least two different types of cDNAs having different nucleotide sequences.
As described above, the core protein (C protein), matrix protein (M protein) and envelope protein (E protein) of the NANBV are included in the region from the 1st (Met) to 389th (Gly) amino acids of SEQ ID NO:2 shown in FIG. 2(1) through FIG. 2(3). Therefore, the above-mentioned epitopes contained in this region, especially epitopes coded for by nucleotide sequences respectively of the 906th to 953rd nucleotides, of the 1020th to 1046th nucleotides and of the 1194th to 1232nd nucleotides of SEQ ID NO: 1, are extremely useful as antigens. The epitopes may be obtained by polypeptide synthesis. The polypeptide synthesis can be conducted by means of a commercially available polypeptide synthesizer, such as polypeptide synthesizer COUPLER 2100 (manufactured and sold by Du Pont, USA) and polypeptide synthesizer 430A (manufactured and sold by Applied Biosystems, USA). The synthesized antigen polypeptide may be used, for example, for producing a vaccine, a diagnostic reagent and an antibody.
In a further aspect of the present invention, there is provided a replicable recombinant comprising a replicable expression vector selected from a plasmid and an animal virus gene and a deoxyribonucleic acid comprising a nucleotide sequence selected from the group consisting of the first nucleotide sequence comprising at least part of a region from the 1st to 1499th nucleotides or at least part of a region from the 1500th to 9416th nucleotides of the non-A, non-B hepatitis virus nucleotide sequence (SEQ ID NO:1) shown in FIG. 2(1) through FIG. 2(16) hereof and a nucleotide sequence obtained by substituting at least one nucleotide of the first nucleotide sequence in accordance with the degeneracy of the genetic code.
The replicable recombinant can be used not only for producing the NANBV antigen polypeptide of the present invention but also for amplifying the NANBV genomic cDNA of the present invention by replication.
In a preferred embodiment of the present invention with respect to the replicable recombinant for amplifying the NANBV genomic cDNA by replication, the first nucleotide sequence comprises at least six nucleotides of the nucleotide sequence of the 1st to 1499th nucleotides or at least six nucleotides of the nucleotide sequence of the 1500th to 9416th nucleotides of SEQ ID NO:1.
In a preferred embodiment of the present invention with respect to the replicable recombinant for producing the NANB antigen polypeptide, the first nucleotide sequence comprises at least twelve nucleotides of the nucleotide sequence of the 333rd to 1499th nucleotides or at least twelve nucleotides of the nucleotide sequence of the 1500th to 9362nd nucleotides of SEQ ID NO:1.
In another preferred embodiment of the present invention with respect to the replicable recombinant for producing the NANBV antigen polypeptide, the first nucleotide sequence is selected from the group consisting of a nucleotide sequence of the 333rd to 422nd nucleotides, a nucleotide sequence of the 333rd to 677th nucleotides, a nucleotide sequence of the 333rd to 1499th nucleotides, a nucleotide sequence of the 474th to 563rd nucleotides, a nucleotide sequence of the 678th to 905th nucleotides, a nucleotide sequence of the 906th to 953rd nucleotides, a nucleotide sequence of the 906th to 1499th nucleotides, a nucleotide sequence of the 1020th 1046th nucleotides, a nucleotide sequence of the 1020th to 1121st nucleotides, a nucleotide sequence of the 1194th to 1232nd nucleotides, a nucleotide sequence of the 1209th to 1322nd nucleotides, a nucleotide sequence of the 1500th to 2519th nucleotides, a nucleotide sequence of the 2520th to 3350th nucleotides, a nucleotide sequence of the 3351st to 5177th nucleotides, a nucleotide sequence of the 4485th to 4574th nucleotides, a nucleotide sequence of the 5178th to 5918th nucleotides, a nucleotide sequence of the 5544th to 5633rd nucleotides, a nucleotide sequence of the 5919th to 6371st nucleotides and a nucleotide sequence of the 6327nd to 9362nd nucleotides of SEQ ID NO:1.
The purified NANBV antigen polypeptide of the present invention is useful as a diagnostic reagent for detecting NANB hepatitis.
The NANBV antigen polypeptide of the present invention can be formulated into a diagnostic reagent as follows. The purified NANBV antigen polypeptide solution obtained above is dispensed in a vessel, such as a vial and an ampul, and sealed. The antigen polypeptide solution put in a vessel may be lyophilized before the sealing, in the same manner as mentioned above. The amount of the NANBV antigen polypeptide put in a vessel is generally about 1 .mu.g to about 10 mg. Alternatively, the NANBV antigen polypeptide may also be adsorbed on the surface of a customarily employed support, such as a microplate, polyethylene beads, filter paper or a membrane.
The determination of the reactivity of the serum with the NANBV antigen polypeptide may be conducted in substantially the same manner as described in Step (V) mentioned above. That is, the determination of the reactively may be conducted by a conventional immunoassay method, such as radioimmunoassay (RIA), enzyme-linked immunosorbent assay (ELISA), fluorescent antibody technique (FA), passive haemagglutination (PHA), reversed passive haemagglutination (rPHA) and the like. The amount of the NANBV antigen polypeptide to be used for the above immunoassay is generally from about 0.1 to about 100 mg/ml of serum. Particularly, the amounts of the NANBV antigen polypeptide to be used for RIA, ELISA, FA, PHA and rPHA are generally from 0.1 to 1 mg/ml, from 0.1 to 1 mg/ml, from 1 to 100 mg/ml, from 1 to 50 mg/ml and from 1 to 50 mg/ml, respectively.
The NANBV antigen polypeptide of the present invention may also be used for screening blood for transfusion. The screening method consists in:
a) isolating serum from whole blood;
b) contacting serum of an unknown blood with an isolated NANBV antigen polypeptide comprising at least one amino acid sequence comprising at least part of an amino acid sequence coded for by a deoxyribonucleic acid comprising a coding region from the 333rd to 9362nd nucleotides of the NANBV nucleotide sequence (SEQ ID NO:1) shown in FIG. 2(1) through FIG. 2(16);
c) determining whether the serum reacts with the NANBV antigen polypeptide;
d) classifying the serum as positive or negative to non-A, non-B hepatitis based on the reactivity; and
e) effecting separation of the blood in accordance with the identification.
The contact of serum of an unknown blood with the NANBV antigen polypeptide of the present invention, and the determination of the reactivity of the serum of the blood with the NANBV antigen polypeptide may be conducted in the same manner as mentioned above with respect to the method for diagnosing NANB hepatitis. By the above method, a blood for transfusion free from the NANBV can be selected.
The polyclonal antibody and monoclonal antibody specific for the NANBV antigen polypeptide of the present invention may be used as an agent for removing NANBV from blood for transfusion. That is, NANBV present in blood can efficiently be removed by the polyclonal antibody or the monoclonal antibody by antigen-antibody reaction.
Further, the NANBV antigen polypeptide of the present invention may advantageously be used as an active ingredient of a vaccine for NANB hepatitis. The vaccine for NANB hepatitis may be prepared as follows. The culturing of a transformant containing a recombinant phage or plasmid carrying the cDNA coding for the NANBV antigen polypeptide, or a cell infected with the recombinant virus carrying the cDNA coding for the NANBV antigen polypeptide is conducted in the same manner as described above to thereby produce the NANBV antigen polypeptide in the culture. For detoxifying the NANBV antigen polypeptide in the culture to secure the safety of the antigen polypeptide and for fixing the antigen polypeptide to stabilize the immunogenicity and the antigenicity of the antigen polypeptide, it is preferred to add a conventional inactivating agent to the culture of the transformant or recombinant virus-infected cell, or to a culture medium obtained by removing the transformant cells or the recombinant virus-infected cell. For example, an inactivating agent, such as formalin, may be added in an amount of from 0.0001 to 0.001 v/v %, followed by incubation at 4 to 37.degree. C. for 5 to 90 days. Then, the resultant culture or culture medium is subjected to purification in the same manner as mentioned above. Thus, an original NANB hepatitis vaccine solution containing the purified NANBV antigen polypeptide is obtained.
The original NANB hepatitis vaccine solution is filtered using a microfilter by a standard method to sterilize the solution. The filtrate is diluted with physiological saline so that the protein concentration is about 1 to about 500 .mu.g/ml as measured by the Lowry method. To the resultant solution is then added aluminum hydroxide gel as an adjuvant so that the concentration of the added gel becomes about 0.01 to about 1.0 mg/ml. As an adjuvant, there may also be employed precipitating depositary adjuvants such as calcium phosphate gel, aluminum phosphate gel, aluminum sulfate, alumina and bentonite, and antibody-production inducing adjuvants such as muramyl peptide derivatives, polynucleotides, Krestin.RTM. (manufactured and sold by Kureha Chemical Industry Co., Ltd., Japan) and picibanil (both of which are an antineoplastic agent). Further, to the mixture, at least one stabilizing agent may be added. As the stabilizing agent, any commercially available stabilizing agent may be used. Examples of stabilizing agents include gelatin and hydrolysates thereof, albumin, saccharides such as glucose, fructose, galactose, sucrose and lactose, and amino acids such as glycine, alanine, lysine, arginine and glutamine.
Then, the thus obtained NANB hepatitis vaccine solution containing a gel-adsorbed NANBV antigen polypeptide is dispensed into a small vessel, such as an ampul and a vial, and sealed. Thus, there is obtained a purified adsorbed NANB hepatitis vaccine comprising an adsorbed NANBV antigen polypeptide.
The NANB hepatitis vaccine solution thus obtained may be lyophilized to obtain the NANB hepatitis vaccine in a dried form so that the product can be transported to and stored at a place of severe climate, for example, in an area in the tropics. The lyophilization may generally be conducted according to a standard method after the liquid adsorbed NANB hepatitis vaccine is dispensed in a vessel such as a vial and an ampul. After lyophilization, a nitrogen gas is introduced in the vessel containing the dried vaccine, followed by sealing. Incidentally, the quality of the vaccine produced is examined in accordance with "Adsorbed Hepatitis B Vaccine", "Dried Japanese Encephalitis Vaccine", and "Adsorbed Pertussis Vaccine" provided for in Notification No. 159 of the Ministry of Health and Welfare, Japan, "Minimum Requirements for Biological Products".
The NANB hepatitis vaccine may be prepared in the form of a mixed vaccine which contains an adsorbed NANBV antigen polypeptide mentioned above and at least one antigen other than the present NANBV antigen polypeptide. As the antigen other than the present NANBV antigen polypeptide, there may be employed any antigens that are conventionally used as active ingredients of the corresponding vaccines insofar as the side effects and adverse reactions caused by such other antigens and the NANBV antigen polypeptide are not additively or synergistically increased by the use of the NANBV antigen polypeptide and such other antigens in combination and the antigenicities and immunogenicities of the NANBV antigen polypeptide and such other antigens are not reduced by the interference between the NANBV antigen polypeptide and other antigens. The number and the types of the antigens which may be mixed with the NANBV antigen polypeptide are not limited insofar as the side effects and adverse reactions are not increased additively or synergistically and the antigenicity and immunogenicity of each of the NANBV antigen polypeptide and such antigens are not reduced as mentioned above. Generally, two to six types of antigens may be mixed with the NANBV antigen polypeptide. Examples of antigens which may be mixed with the present NANBV antigen polypeptide, include detoxified antigens, inactivated antigens or toxoids which are derived from Japanese encephalitis virus, HFRS (hemorrhagic fever with renal syndrome) virus, influenza virus, parainfluenza virus, hepatitis B virus, dengue fever virus, AIDS virus, Bordetella pertussis, diphtheria bacillus, tetanus bacillus, meningococcus, pneumococcus and the like.
Generally, the vaccine comprising the NANBV antigen polypeptide of the present invention may be contained and sealed in a vial, an ampul or the like. The vaccine of the present invention may generally be administered in the form of a liquid or suspension. In the case where the vaccine is in a dried form, the vaccine is dissolved or suspended in sterilized distilled water before administration, the amount of the distilled water being such that the volume becomes the original volume before being subjected to lyophilization. Generally, the vaccine may be administered subcutaneously. The dose of the vaccine per person may generally be about 0.5 ml. In general, the dose of the vaccine per child may be half as much as that of the vaccine per adult. The vaccine may generally be administered twice at an interval of about one week to one month and then, about half a year later, administered once more.
Further, the NANBV antigen polypeptide may be used for preparing an antibody, such as a polyclonal antibody and a monoclonal antibody, specific for the NANBV antigen polypeptide. For example, a polyclonal antibody specific for the NANBV antigen polypeptide may be prepared by a conventional method as follows. The purified NANBV antigen polypeptide of the present invention is inoculated subcutaneously, intramuscularly, intraperitoneally or intravenously to an animal, such as mouse, guinea pig and rabbit. The inoculation of the NANBV antigen polypeptide is generally conducted several times at intervals of 1 to 4 weeks, to thereby completely immunize the animal. In order to enhance the immunizing effect, a conventional and commercially available adjuvant may be used. Then, blood serum is collected from the immunized animal and an anti-NANBV antigen polypeptide polyclonal antibody is isolated and purified from the blood serum according to a standard method.
On the other hand, a monoclonal antibody specific for the NANBV antigen polypeptide may be prepared by a conventional method as described, for example, in Cell Technology, 1, 23-29 (1982). For example, splenic cells obtained from a mouse immunized with the purified NANBV antigen polypeptide are fused with commercially available mouse myeloma cells by cell fusion technique, to obtain hybridomas. The hybridomas are screened to obtain a hybridoma capable of producing an antibody reactive with the NANBV antigen polypeptide. The obtained hybridoma is cultured in a standard method. From the supernatant of the culture, an anti-NANBV antigen polypeptide monoclonal antibody is isolated and purified by a standard method.
The above-mentioned polyclonal antibody and monoclonal antibody may also be used as a diagnostic reagent for diagnosing NANB hepatitis. The diagnosis of NANB hepatitis using the antibody may be conducted by immunoassay in substantially the same manner as mentioned above with respect to the diagnosis of NANB hepatitis using the NANBV antigen polypeptide. By the use of the polyclonal antibody or the monoclonal antibody, the identification and quantification of the NANBV antigen polypeptide present in a liver tissue and blood can be conducted.
The NANBV genomic cDNA of the present invention can be prepared by digesting the NANBV genomic cDNA clone defined in the present invention with an appropriate restriction enzyme. Also, the NANBV genomic cDNA of the present invention can be prepared by the technique of DNA synthesis in accordance with the nucleotide sequence (SEQ ID NO:1) shown in FIG. 2(1) to FIG. 2(16) of the present application. The preparation of the NANBV genomic cDNA by way of DNA synthesis can be performed by means of a customary DNA synthesizer, such as DNA synthesizer Model 380B (manufactured and sold by Applied Biosystem, U.S.A.) and DNA Synthesizer Model 8700 (manufactured and sold by Biosearch, U.S.A.). The NANBV genomic cDNA of the present invention can be used to conduct the genetic diagnosis of NANBV infection. That is, the NANBV genomic cDNA of the present invention can be used as a primer for polymerase chain reaction (PCR) in the detection of an NANBV gene in the body fluid or cells from a patient. For the diagnosis by polymerase chain reaction, the NANBV genomic cDNA is used in an amount of 10 to 100 ng.
The NANBV genomic cDNA of the present invention may also be used for diagnosing NANB hepatitis by hybridization technique. That is, the NANBV genomic cDNA is labeled with, for example, biotin, alkaline phosphatase, radioisotope .sup.32 P or the like and used as a probe for hybridization. The cDNA to be used for the diagnosis by hybridization technique may be prepared by a standard method, for example, as follows. The recombinant phage containing the NANBV cDNA obtained in Step (V) mentioned above is digested with an appropriate restriction enzyme to cut off the DNA fragment containing the NANBV cDNA. The obtained DNA fragment is ligated to a commercially available replicable cloning plasmid to obtain a recombinant plasmid containing the DNA fragment. The recombinant plasmid is introduced in a host cell to form a transformant and the transformant is cultured to multiply the recombinant plasmid. The multiplied recombinant plasmid is isolated from the transformant and digested with a restriction enzyme. The resultant digest is subjected to low-melting point agarose gel electrophoresis to isolate and purify the cDNA coding for the NANBV antigen polypeptide. The thus obtained cDNA is labeled with biotin, alkaline phosphatase, radioisotope .sup.32 P or the like. The labeling of the cDNA may be conducted by using a commercially available nick translation kit or multiprime DNA labeling system (manufactured and sold by, for example, Amersham, England; Nippon Gene Co., Ltd., Japan; and the like). The labeled cDNA is put in a vessel having a volume of about 5 to 20 ml, such as a vial or an ampul, and sealed. The amount of the labeled cDNA put in a vessel is generally 1 to 100 .mu.g per vessel. The labeled cDNA may be contained in the vessel in the form of a solution. Alternatively, the labeled cDNA may be contained in the vessel in a lyophilized state. The diagnosis of NANB hepatitis by the use of the labeled cDNA is conducted by a standard hybridization method. That is, plasma, serum or leukocytes obtained from a patient is placed in contact with the labeled cDNA and an RNA hybridized with the labeled cDNA is detected. The detection of the RNA hybridized with the labeled cDNA may be conducted by a standard method. When the cDNA is labeled with an enzyme, the detection is conducted by enzyme immunoassay. When the cDNA is labeled with a radioisotope, the detection is conducted by, for example, scintillation counting.
The NANBV genomic cDNA of the present invention is excellent in reliability and contains the entire region of the open reading frame of the NANBV gene.
The NANBV antigen polypeptide of the present invention is specifically reactive with the NANBV. Therefore, when the NANBV antigen polypeptide is used as a diagnostic reagent, the diagnosis of NANB hepatitis can be conducted easily with high reliability. Further, when the NANBV antigen polypeptide of the present invention is used for screening blood for transfusion, blood which is infected by NANBV can be selected easily with high reliability and removed from blood not infected by NANBV. Therefore, the post-transfusion. NANB hepatitis can be prevented.
Further, the NANBV antigen polypeptide of the present invention may advantageously be used as an active ingredient of a vaccine for preventing NANB hepatitis.
Further, by the use of the NANBV antigen polypeptide of the present invention, an antibody, particularly monoclonal antibody, specific for NANBV can easily be prepared. The antibody specific for NANBV can advantageously be used as not only a diagnostic reagent for detecting NANB hepatitis, but also an agent for removing NANBV from blood for transfusion.
Furthermore, it should be noted that the NANBV antigen polypeptide of the present invention is not produced by the infection of an animal with a virus, but produced by gene expression of the DNA coding for the present antigen polypeptide in a host cell. Hence, the possibility of infection during the steps for production of the present antigen polypeptide is substantially eliminated. Also, the production cost can be decreased. Moreover, since all of the materials used in the production process, e.g., medium for the incubation system, are well-known in respect of the composition thereof, purification is facile and an antigen polypeptide product having high purity can be obtained.
PREFERRED EMBODIMENT OF THE INVENTION
The present invention will now be described in detail with reference to the following Examples, which should not be construed to be limiting the scope of the present invention.
EXAMPLE 1
Step 1 (Preparation of a plasma-derived RNA for producing cDNA, which is complementary to NANBV genome RNA)
In order to obtain NANBV from plasma, 4.8 liters of human plasma exhibiting a glutamic=pyruvic transaminase (GPT) activity of 35 IU/ or more (as measured by the method of Wroblewski, F & J. S. LaDue: Serum glutamic-pyruvic transaminase in cardiac and hepatic disease. Proc. Soc. Exp. Biol. Med., 91:569, 1956) was superposed on a 30% (w/w) aqueous sucrose solution, and subjected to centrifugation under 48,000 x g at 4.degree. C. and for 13 hours to obtain a precipitate. The precipitate was suspended in an aqueous solution containing 50 mM Tris.HCl (pH 8.0) and 1 mM EDTA, and once more subjected to centrifugation under 250,000 x g at 4.degree. C. and for 3 hours to thereby obtain a precipitate. The obtained precipitate was dissolved in 75 ml of 5.5M GTC solution containing 5.5M quanidine thiocyanate, 20 mM sodium citrate (pH 7.0), 0.05% sarkosyl (sodium lauryl sarcosinate) and 0.1M 2-mercaptoethanol. The resultant solution was superposed on 16 ml of CsTFA-0.1M EDTA solution (.rho.=1.51), and subjected to centrifugation under 140,000 x g at 15.degree. C. and for 20 hours to thereby obtain a precipitate of RNA. The supernatant containing proteins and DNA was removed by suction, and the precipitate was dissolved in 200 .mu.l of TE 10 mM Tris.HCl, pH 8.0 and 1 mM EDTA solution. 20 .mu.l of 3M sodium chloride and ethanol were added to the solution, and allowed to stand still at -70.degree. C. for 90 minutes. The mixture was centrifuged under 12,000 X g at 4.degree. C. and for 30 minutes to obtain a precipitate. The precipitate was dissolved in TE, and sodium chloride and ethanol were added in the same manner as mentioned above. The mixture was allowed to stand still at -70.degree. C. to obtain a precipitate. The precipitate was dissolved in 10 .mu.l of TE to thereby obtain a purified RNA.
Step 2 (Preparation of a liver-derived RNA for producing a cDNA, which is complementary to NANBV genome RNA)
NANBV genome RNA was prepared from a liver tissue cut off from a NANBV hepatitis patient by the method of Okayama et al. (see H. Okayama, M. Kawaichi, M. Brownstein, F. Lee, T. Yokota, and K. Arai: High-Efficiency Cloning of Full-Length cDNA; Construction and Screening of cDNA Expression Libraries for Mammalian Cells, Methods in Enzymology 154.3-28, 1987).
Illustratively state, 1 g of liver tissue was cut into small pieces. The small pieces were suspended in 100 ml of 5.5M GTC solution as used in Step 1, and homogenized by means of a Teflon-glass homogenizer. Subsequently, the introduction of the homogenate into a syringe having #18 needle and the discharge of the homogenate from the syringe through the needle were repeated to thereby mechanically split DNA. The resultant homogenate was centrifuged under 1,500 x g (lower centrifugal force) at 4.degree. C. and for 15 minutes to thereby obtain a supernatant. The supernatant was superposed on CsTFA solution and centrifuged in substantially the same manner as described in Step 1 to thereby obtain a precipitate as an RNA fraction. The thus obtained precipitate was suspended in 0.4 ml of 4M GTC solution. 10 .mu.l of 1M acetic acid and 300 .rho.l of ethanol were added to the suspension, and allowed to stand still at a temperature of -20.degree. C. for at least 3 hours to thereby obtain a precipitate of RNA. The precipitate was separated by centrifugation under 12,000 x g at a temperature of 4.degree. C. and for 10 minutes, and dissolved in 1 ml of TE solution. 100 .mu.l of 2M sodium chloride solution and 3 ml of ethanol were added to the solution, and the mixture was allowed to stand at -20.degree. C. for 3 hours. The resultant precipitate was collected by centrifugation and dissolved in 10 .mu.l of TE to thereby obtain a purified, liver-derived RNA.
Step 3 (Preparation of a double-stranded cDNA using a cDNA synthesis kit)
A double-stranded cDNA was prepared using a commercially available cDNA synthesis kit (manufactured and sold by Amersham International, England).
Illustratively state, 0.75 .mu.g of the purified RNA obtained in Step 1 and 2 .mu.l of random hexanucleotide primer and 2 .mu.l of reverse transcriptase taken from the reagents included in the kit were put in a reaction tube. Then, distilled water was added in an amount such that the total volume of the resultant mixture became 20 .mu.l. The mixture was incubated at 42.degree. C. for 40 minutes, thereby preparing a first strand of cDNA. Subsequently, a second strand of cDNA was synthesized while cooling the reaction mixture in ice water, as follows. To 20 .mu.l of the reaction mixture were added 37.5 .mu.l of buffer for second strand synthetic reaction, 1 .mu.l of E. coli ribonuclease H and 6.6 .mu.l of DNA polymerase I, which were taken from the reagents included in the kit, followed by addition of 34.9 .mu.l of distilled water. The mixture was incubated at 12.degree. C. for 60 minutes, 22.degree. C. for 60 minutes and at 70.degree. C. for 10 minutes. Then, the mixture was once more cooled with ice water. 1 .mu.l of T4 DNA polymerase was added, incubated at a temperature of 37.degree. C. for 10 minutes, and 4 .mu.l of 0.25M EDTA (pH 8.0) was added to thereby terminate the reaction. The reaction mixture was mixed well with a mixture of phenol and chloroform, and centrifuged under 12,000 x g for one minute to thereby separate an aqueous layer. The aqueous layer was again subjected to the same extraction as mentioned above, and an equal amount of chloroform was added. The mixture was agitated well and centrifuged to separate an aqueous layer. Subsequently, an equal amount of 4M ammonium acetate and a two-fold amount of ethanol were added to the aqueous layer, and the mixture was cooled to -70.degree. C., thereby obtaining a precipitate of purified double-stranded cDNA. The precipitate was dissolved in 50 .mu.l of 2M ammonium acetate. To the mixture, 100 .mu.l of ethanol was added, and the resultant mixture was cooled to -70.degree. C. to thereby obtain a precipitate. The precipitate was collected by centrifugation under 12,000 x g for ten minutes. The collected precipitate was dried and then, dissolved in 20 .mu.l of TE.
Step 4 (Preparation of a double-stranded cDNA by the Polymerase Chain Reaction (PCR) method)
The cDNAs which were prepared by means of a reverse transcriptase using as templates the RNAs prepared in Step 1 and Step 2, were individually amplified by the PCR method (see Saiki, R. K., Gelfand, D. H., Stoffer, S., Scharf, S. J., Higuchi, R., Horn, G. T., Mullis, K. B., and Erlich, H. A., Primer-directed enzymatic amplification of DNA with a thermostable DNA Polymerase, Science 239:487-491, 1988). That is, 5 to 1,000 ng of the RNA was incubated in 20 .mu.l of a reverse transcriptase solution containing 50 mM Tris.HCl (pH 8.3), 40 mM KCl, 6 mM MgCl.sub.2, 1 .mu.M 3'-primer [synthesized oligonucleotide comprised of 25 nucleotides of nucleotide numbers 7949 to 7973 in FIG. 2(14)], 10 mM dNTP, and 0.5 unit of reverse transcriptase (product of New England Bio Lab., U.S.A.) at 37.degree. C. for 30 minutes. To the resultant mixture was added 80 .mu.l of a PCR reaction solution containing 18 mM Tris.HCl (pH 8.3), 48 mM KCl, 1.5 mM MgCl.sub.2, 0.6 .mu.M each of 5'-primer [synthesized oligonucleotide comprised of 25 nucleotides of nucleotide numbers 7612 to 7636 in FIG. 2(13)]and the above-mentioned 3'-primer, 10 mM dNTP and 2.5 units of Taq DNA polymerase (manufactured and sold by Perkin Elmer Cetus Co., Ltd., U.S.A.). The mixture was subjected to incubation at 94.degree. C. for one minute, at 50.degree. C. for 2 minutes and at 72.degree. C. for 3 minutes. This incubation was repeated 40 times. The resultant mixture was subjected to electrophoresis using agarose gel, thereby obtaining amplified cDNA. The amplified cDNA was subjected to phenol treatment, ethanol precipitation and drying. The dried cDNA was dissolved in 10 .mu.l of TE.
Step 5 (Preparation of a cDNA library using lambda gt11)
Using a commercially available cDNA cloning kit (manufactured and sold by Amersham International, England), a cDNA library was prepared. That is, to 130 ng of cDNA prepared in Step 3 were added 2 .mu.l of L/K buffer, 2 .mu.l of EcoRI adaptor and 2 .mu.l of T4 DNA ligase, which were taken from the reagents included in the cloning kit. Distilled water was added to the solution in an amount such that the total volume of the resultant mixture became 20 .mu.l. The mixture was incubated at a temperature of 15.degree. C. for a period of from 16 to 20 hours, and 2 .mu.l of 0.25M EDTA was added thereto, to thereby terminate the reaction. Subsequently, the mixture was passed through a size fractionating column included in the kit, thereby removing EcoRI adaptors which were not ligated to the cDNA. To 700 .mu.l of the cDNA having EcoRI adaptor ligated thereto were added 83 .mu.l of L/K buffer and 8 .mu.l of T4 polynucleotidekinase. The mixture was incubated at a temperature of 37.degree. C. for 30 minutes. The resultant mixture was subjected to phenol extraction twice, concentration to 350 to 400 .mu.l by means of butanol and then ethanol precipitation, thereby obtaining a precipitate. The precipitate was dissolved in 5 .mu.l of TE.
Subsequently, in order to insert the cDNA having EcoRI adaptor ligated thereto to the EcoRI site of cloning vector lambda gt11, 1 .mu.l of L/K buffer, 2 .mu.l (1 .mu.g) lambda gt11 arm DNA and 2 .mu.l of T4 DNA ligase were added to 1 .mu.l (10 ng) of the above-mentioned cDNA having EcoRI adaptor ligated thereto. Distilled water was added to the mixture in an amount such that the total volume of the mixture became 10 .mu.l. The mixture was incubated at a temperature of 15.degree. C. for a period of from 16 to 20 hours. Thus, a recombinant lambda gt11 DNA solution was prepared. Further, a recombinant lambda phage was obtained by in vitro packaging using a commercially available in vitro packaging kit (manufactured and sold by Stratagene Co., Ltd., U.S.A.) including Gigapack II Gold solutions A and B, SM buffer and chloroform. That is, 10 .mu.l of Gigapack II Gold solution A and 15 .mu.l of Gigapack II Gold solution B were added to 4 .mu.l of the above-mentioned recombinant lambda gt11 DNA solution. The mixture was incubated at 22.degree. C. for 2 hours. After the incubation, 470 .mu.l of SM buffer and 10 .mu.l of chloroform were added to thereby obtain a recombinant phage, which was stored at 4.degree. C.
Step 6 (Cloning of cDNA using E. coli plasmid pUC19)
Using a commercially available DNA ligation kit (manufactured and sold by Takara Shuzo Co., Ltd., Japan) including solutions A and B, the cDNA was inserted in E. coli plasmid pUC19 (C. Yanishi-Perron, J. Vieira, J. Messing, Gene 33, 103, 1985), and cloned in E. coli. That is, 40 .mu.l of solution A and 10 .mu.l of solution B were added to 5 .mu.l of the cDNA prepared by polymerase chain reaction (PCR) in Step 4 and 4 .mu.l (50 ng) of plasmid pUC19 DNA which had been digested with restriction enzyme SmaI and dephosphorylated. The mixture was incubated at a temperature of 15.degree. C. for 16 hours. E. coli strain JM 109 (see Messing, J., Crea, R., and Seeburg, P. H., Nucleic Acids Res. 9, 309, 1981) was transformed with the above-obtained plasmid DNA according to the calcium chloride method (see Mandel, M. and A. Higa, J. Mol. Biol., 53, 154, 1970). Thus, a transformed E. coli containing the plasmid having the cDNA ligated thereto was obtained.
Step 7 (Screening of clone having NANBV gene from a cDNA library)
E. coli strain Y 1090 (see Richard A. Yound and Ronald W. Davis, Science, 222, 778, 1983) was cultured in 50 ml of LBM medium containing 1% tryptone, 0.5% yeast extract, 1% sodium chloride, 50 .mu.g/ml amplicillin and 0.4% maltose at a temperature of 37.degree. C. The E. coli cells in a logarithmic growth phase were suspended in 15 ml of 10 mM magnesium sulfate cooled with ice. The phage solution obtained in Step 5 was diluted with SM buffer containing 0.1M sodium chloride, 8 mM magnesium sulfate, 50 mM Tris.HCl (pH 7.5) and 0.01% gelatin. 0.1 ml of the diluted phage solution was mixed with an equal volume of the above-mentioned E. coli cell suspension, and the mixture was incubated at a temperature of 37.degree. C. for 15 minutes. To the mixture was added 4 ml of soft agar medium heated to 45.degree. C. and containing 1% tryptone, 0.5% yeast extract, 0.5% sodium chloride, 0.25% magnesium sulfate and 0.7% agar (pH 7.0). The mixture was spread on L-agar plate containing 1% tryptone, 0.5% yeast extract, 1% sodium chloride, 1.5% agar and 100 .mu.g/ml ampicillin (pH 7.0), and incubated at a temperature of 42.degree. C. for 3 hours. Subsequently, 10 mM IPTG (isopropyl .beta.-D-thiogalactopyranoside) was infiltrated into a nitrocellulose filter, and the nitrocellulose filter was dried and closely contacted with the L-agar plate. The plate was incubated at a temperature of 37.degree. C. for 3 hours. The filter was separated, and washed with TBS buffer three times. The washed filter was immersed in 2% bovine serum albumin solution, and incubated at room temperature for one hour. 1/20 volume of E. coli lysate solution included in a commercially available immunoscreening kit (manufactured and sold by Amersham International, England) was added to pooled serum from NANB hepatitis patients, and incubated at room temperature for 30 minutes. Thereafter, the serum was diluted to 50-fold with 0.2% bovine serum albumin-added TBS buffer, and the filter was immersed in the diluted serum solution, and incubated at room temperature for one hour.
The resultant filter was washed four times with a TBS buffer containing 0.05% Tween 20. The washed filter was immersed in an antibody solution which had been prepared by diluting a peroxidase-labeled anti-human IgG (manufactured and sold by Cappel Co., Ltd., Germany) 1,000-fold for one hour. The filter was washed with the above-mentioned Tween-TBS buffer, and immersed in a solution prepared by adding 0.4 ml of DAB (3,3'-diaminobenzidine tetrahydrochloride) and 15 .mu.l of a 30% aqueous hydrogen peroxide solution to 50 ml of a TBS buffer, followed by incubation at room temperature for 5 to 30 minutes to allow color development. The resultant filter was completely washed with distilled water to terminate the reaction.
By the above-mentioned procedure, the obtained plaques were purified. As a result, 9 positive clones were isolated, which were, respectively, designated as BK 102, BK 103, BK 105, BK 106, BK 108, BK 109, BK 110, BK 111 and BK 112. All of these clones did not react with serum from a healthy human, but reacted with serum from a patient suffering from NANB hepatitis. See Table 1.
TABLE 1______________________________________Reactivity between the serum obtained from a patient suffering from NANB hepatitis and the recombinant lambda gt11 phage clone Serum from Serum from NANB Clone healthy person hepatitis patient______________________________________BK 102 0/10* 10/11 BK 103 0/10 9/11 BK 105 0/10 11/11 BK 106 0/10 11/11 BK 108 0/10 9/11 BK 109 0/10 9/11 BK 110 0/10 9/11 BK 111 0/10 9/11 BK 112 0/10 10/11______________________________________ *the number of positive samples/the number of specimens.
Step 8 (Determination of the nucleotide sequence of the obtained clones)
Recombinant phage DNAs of clones BK 102 to BK 112 were collected, and the collected DNAs were digested with restriction enzyme EcoRI. Then, cDNA fragments of NANBV were isolated and the isolated cDNAs were individually inserted into plasmid pUC19 at EcoRI site. Using the plasmids, E. coli strain JM 109 was transformed in substantially the same manner as in Step 7. Plasmid DNAs were obtained from the transformed E. coli and purified. The nucleotide sequence of each of the NANBV cDNAs was determined using 7-DEAZA sequencing kit (manufactured and sold by Takara Shuzo Co., Ltd., Japan; see Mizusawa, S., Nishimura, S. and Seela, F. Nucleic Acids Res., 14, 1319, 1986). The relationship between the nucleotide sequences of the obtained cDNA clones is shown in FIG. 1(1).
Step 9 9 (Cloning of NANBV cDNA clones from a cDNA library by Genomic Walking)
Probes were prepared by labeling with .sup.32 P-dCTP the cDNA fragments of clone BK 102, clone BK 106 and clone BK 112 which were obtained in Step 8. Using the probes, phage clones containing NANBV cDNAs were obtained by hybridization from the cDNA library of cloning vector lambda gt11 obtained in Step 5 and the above-mentioned probes. That is, plasmid DNAs were prepared from the transformed E. coli with clone BK 102, clone BK 106 and clone BK 112 obtained in Step 8 by the alkali method (see T. Maniatis, E. G. Fritsch, and J. Sambrook: Isolation of Bacteriophage .lambda. and Plasmid DNA: "Molecular Cloning", Cold Spring Harbor Lab., pp 75-96.).
Plasmid DNA of clone BK 102 was digested with restriction enzymes NcoI and HincII, and the resultant 0.7 kb fragments having been on the 5'-terminus side of the DNA were subjected to electrophoresis with agarose gel, and collected. Plasmid DNAs of clone BK 106 and clone BK 112 were digested with restriction enzyme NcoI. In the same manner as mentioned above, 1.1 kb DNA fragments were collected from clone BK 106, and 0.7 kb fragments having been on the 3'-terminus side were collected from clone BK 112. 25 ng to 1 .mu.g of DNA fragments were incubated with [.alpha.-.sup.32 P]dCTP (3000 Ci/mmol; manufactured by Amersham Co., Ltd., England) at a temperature of 37.degree. C. for a period of from 3 to 5 hours, using commercially available DNA labeling kit (manufactured by Nippon Gene Co., Ltd.). Thus, probes for hybridization were prepared.
Subsequently, the cDNA library phage obtained in Step 5 was incubated at a temperature of 42.degree. C. in L-agar medium for 3 hours, as described in Step 7. Further, the phage was incubated at a temperature of 37.degree. C. for 3 hours, and was cooled. A nitrocellulose filter was disposed on the mixture, and was allowed to stand still for a period of from 30 to 60 seconds. Thus, the phage was adsorbed onto the filter.
The filter was subjected to alkali denaturation for a period of from 1 to 5 minutes using an aqueous solution containing 0.5N sodium hydroxide and 1.5M sodium chloride and to the neutralization with an aqueous solution containing 0.5M Tris.HCl (pH 8.0) and 1.5M sodium chloride for a period of from 1 to 5 minutes. The filter was washed with 2 x SSC solution containing 0.3M sodium chloride and 0.03M sodium citrate, air dried, and baked at a temperature of 80.degree. C. for 2 hours.
The filter was incubated at a temperature of 42.degree. C. for 6 hours in a solution for hybridization containing 50% formamide, 5 x SSC, 5 x Denhart solution, 50 mM phosphoric acid-citric acid buffer (pH 6.5), 100 .mu.g/ml trout sperm DNA and 0.1% SDS. Then, the filter was immersed in 300 ml of the hybridization solution having 1 ml of the above-mentioned probe of about 4.times.10.sup.8 cpm/ml added thereto, and incubated at a temperature of 42.degree. C. for 16 to 20 hours. The filter was washed with an SDS solution containing 0.1% 2 x SSC four times and with an SDS solution containing 0.1% 0.1 x SSC twice. After the washing, the filter was dried, and was subjected to autoradiography. Thus, hybridization positive clones were isolated. As a result, 27 clones being reactive with the probe derived from clone BK 102, 14 clones being reactive with the probe derived from clone BK 106 and 13 clones being reactive with the probe derived from clone BK 112, were obtained, which were respectively designated as BK 114 to BK 169.
The nucleotide sequence of each of clones BK 114 to BK 169 was determined according to the method described in Step 8, followed by mapping for each of the clones. As a result, a map of nucleotide sequence having a length of about 9.5 kb considered to be the approximately total length of the NANBV genome was obtained [see FIG. 1(2)].
Clone BK 157 located on the 5' terminus side was digested with restriction enzyme KpnI to thereby collect a 0.55 kb fragment having been on the 4'-terminus side. Also, clone BK 116 located on the extreme 3'-terminus side was digested with restriction enzymes HpaI and EcoRI to thereby collect a 0.55 kb fragment having been on the 3'-terminus side. A probe labeled with .sup.32 P was prepared in the same manner as described above, and the cDNA library phage obtained in Step 5 was subjected to plaque hybridization. As a result, three new additional clones were separated by the probe derived from the clone BK 157. These new clones were, respectively, designated as clones BK 170, BK 171 and BK 172.
Step 10 (Analysis of the nucleotide sequence of cDNA)
The entire nucleotide sequence (SEQ ID NO:1) of NANBV gene was determined from the nucleotide sequences of the clones obtained in Steps 8 and 9, and shown in FIGS. 2(1) to 2(16). From the Figures, it was assumed that the cloned genomic cDNAs of NANBV were composed of 9416 nucleotides, wherein there was an open reading frame composed of 9030 nucleotides coding for a protein composed of 3010 amino acid residues. The hydrophilicity/hydrophobicity pattern of this protein was similar to that of flavivirus as already reported (see H. Sumiyoshi, C. Mori, I. Fuke et al., Complete Nucleotide Sequence of the Japanese Encephalitis Virus Genome RNA. Virology, 161, 497-510, 1987). Clone BK 157 covers nucleotide numbers 1 to 1962 of FIGS. 2(1) to 2(16), clone BK 172 covers nucleotide numbers 5 to 366, clone BK 153 covers nucleotide numbers 338 to 1802, clone BK 138 covers nucleotide numbers 1755 to 5124, clone BK 108 covers nucleotide numbers 6886 to 8344 and clone BK 166 covers nucleotide numbers 8082 to 9416. They are preserved as Escherichia coli BK 108 (deposited at Fermentation Research Institute, Japan under accession number FERM BP-2971), BK 129 (deposited at Fermentation Research Institute, Japan under accession number FERM BP-2972), BK 138 (deposited at Fermentation Research Institute, Japan under accession number FERM BP-2973), BK 153 (deposited at Fermentation Research Institute, Japan under accession number FERM BP-2974), BK 157, BK 166 (deposited at Fermentation Research Institute, Japan under accession number FERM BP-1975), and BK 172 (deposited at Fermentation Research Institute, Japan under accession number FERM BP-2976), respectively.
Step 11 (Production of NANBV-related antigens in E. coli, which antigens are related with the antibody-response accompanying NANBV infection)
Respective cDNAs of clone BK 106, clone BK 111 and clone BK 112 each obtained in Step 8 and cDNA of clone BK 147 obtained in Step 9 were individually inserted into plasmids, and the thus obtained plasmid DNAs were collected by the conventional alkali method. Subsequently, the collected DNA of clone BK 106 was digested with restriction enzymes EcoRI and ClaI to thereby obtain 0.5 .mu.g of a DNA fragment of 0.34 kb in length. The thus obtained DNA fragment was incubated at 37.degree. C. for 60 minutes in a T4 DNA polymerase solution containing 67 mM Tris.HCl (pH 8.8), 6.7 mM magnesium chloride, 16.6 mM ammonium sulfate, 10 mM 2-mercaptoethanol, 6.7 .mu.M EDTA, 0.02% bovine serum albumin, 0.3 mM dNTP and 2-5 units of T4 DNA polymerase, thereby rendering both terminals blunt. The DNA of clone BK 102 was digested with restriction enzyme BamHI to thereby collect 0.5 .mu.g of a DNA fragment of 0.7 kb in length, and the terminals of the DNA fragment were rendered blunt using T4 DNA polymerase in substantially the same manner as mentioned above. The DNA of clone BK 147 was digested with restriction enzyme Sau3AI to thereby obtain 0.5 .mu.g of a DNA fragment of 1 kb in length and the terminals of the DNA fragment were rendered blunt in the same manner as mentioned above. Also, the DNA of clone BK 111 was digested with restriction enzyme EcoRI to thereby obtain 0.5 .mu.g of a DNA fragment of 1 kg in length, and the terminals of the DNA fragment were rendered blunt in substantially the same manner as mentioned above. Subsequently, the DNA of expression vector pKK 233-2 (Amann, E. and J. Brosius. ATG vector for regulated high-level expression of cloned genes in Escherichia coli. Gene, Vol. 40, 183, 1985) was digested with restriction enzyme HindIII. 2 .mu.g of the resultant DNA was incubated at 37.degree. C. for 20 minute sin a S1 nuclease solution containing 0.3 M sodium chloride, 50 mM sodium acetate (pH 4.5), 1 mM zinc sulfate and 100-200 units of S1 nuclease, and the reaction was terminated by adding 1/10 volume of each of 0.12 M EDTA and 1 M Tris.HCl solution (pH 9.0). Then, phenol extraction was performed, and the vector DNA having blunt terminals was precipitated by ethanol and collected. On the other hand, the DNA of vector pKK 233-2 was digested with restricted with restriction enzyme PstI, and the digested DNA was purified by extraction with phenol and precipitation from ethanol. The terminals of 2 .mu.g of the purified vector DNA which had been cleaved by restriction enzyme PstI were rendered blunt by the above-mentioned T4 DNA polymerase reaction. The thus obtained DNA fragments derived from clone BK 106 and clone BK 111 were each cleaved with restriction enzyme HindIII. 0.5 .mu.g of each of the cleaved DNA fragments was mixed with 0.5 .mu.g of a vector DNA having blunt terminals. The DNA fragments derived from clone BK 102 and clone BK 147 were each cleaved with restriction enzyme PstI. 0.5 .mu.g of each of the claved DNA fragments was mixed with 0.5 .mu.g of a vector DNA having terminals thereof rendered blunt. The volume of each of the mixtures was adjusted to 20 .mu.l by adding 2 .mu.l of 10.times. ligation solution containing 500 mM Tris.HCl (pH 7.5), 100 mM magnesium chloride, 100 mM DTT and 10 mM ATP, 300-400 units of T4 DNA ligase and distilled water. The mixtures were incubated at 14.degree. C. for 12-18 hours, thereby obtaining plasmids, which were respectively designated as pCE-06, pE-11, pB-02 and pS-09. Using each of these plasmid DNAs, E. coli strain JM 109 was transformed in substantially the same manner as described in Step 6, thereby obtaining transformed E. coli. The transformed E. coli was cultured at 37.degree. C. in LB medium (pH 7.5) containing 1 (w/v) % trypton, 0.5 (w/v) % yeast extract and 1 (w/v) % sodium chloride, and when it was in logarithmic growth phase, 1 mM IPTG (isopropyl-.beta.-D-thiogalactopyranoside) was added to the medium. The culturing was further continued for 3 hours. Then, E. coli cells were collected by centrifugation (10,000.times.g for 15 minutes), and the collected cells were lysed in 50 mM Tris.HCl (pH 8.0). The mixture was subjected to ultrasonic treatment (20 KHz, 600 W, 5 minutes), and centrifuged at 10,000.times.g for 15 minutes to thereby obtain a supernatant fraction and a precipitate fraction. Each of the fractions was dissolved in a sample buffer containing of 20 (v/v) % glycerol, 0.1 M Tris.HCl (pH 6.8), 2 (w/v) % SDS, 2 (v/v) % 2-mercaptoethanol and 0.02% BPB, heated at 100.degree. C. for 3 minute, and subjected to electrophoresis using 0.1% SDS-7.5% polyacrylamide gel to separate protein. After the electrophoresis, the protein was transferred to a nitrocellulose filter by trans blot cell (manufactured and sold by BIO.RAD Co., Ltd., U.S.A.). The filter was immersed in 3% gelatin solution, and allowed to stand still for 60 minutes. The filter was incubated together with serum from a patient suffering from NANB hepatitis, which had been diluted 100-fold, for 2 to 3 hours at room temperature. The filter was washed with distilled water and then with TTBS solution containing 0.02 M Tris.HCl (pH 7.5), 0.5 M sodium chloride and 0.05 (v/v)% Tween 20. Subsequently, the washed filter was immersed in a 2,000 fold-diluted solution of peroxidase-labeled anti-human IgG antibody, and incubated at room temperature for 90 minutes. The filter was washed with distilled water and then with TTBS solution. The washed filter was immersed in a buffer having, added thereto, coloring agent DAB and 30%, based on substrate, hydrogen peroxide as described in Step 7 for 5 to 30 minutes, following by washing with water, to terminate the reaction.
As a result, as shown in Table 2, all of the antigens produced by the plasmids specifically react with serum from a patient suffering from NANB hepatitis, thereby demonstrating that the proteins produced by the cDNAs inserted in the plasmids are clinically important.
TABLE 2______________________________________Reactivity evaluated by the Western blot method between proteins produced by various plasmids and sera from a patient suffering from NANB hepatitis. Serum from Serum from origin of NANB hepati- healthy Plasmid cDNA Extract titis patient human______________________________________PCE-066 BK 106 S .+-. - P + - pE-11-89 BK 111 S .+-. - P + - pB-02-10 BK 102 S + - P - - ps-09-07 BK 109 S .+-. - P + - pKK 233-3 -- S - - P - -______________________________________ S: Supernatant by centrifugation P: Precipitate by centrifugation +: positive .+-.: slightly positive -: negative
Step 12 (Purification of NANBV-related antigens produced by E. coli and reactivity thereof with serum from a patient suffering form hepatitis)
The usefulness of the protein produced by the cDNA which was inserted into an expression vector was demonstrated by purifying the protein and using the purified protein as an antigen for ELISA or radioimmunoassay. That is, the lysate of the transformed E. coli which was obtained in Step 11 was subjected to centrifugation at 10,000.times.g for 15 minutes, thereby obtaining a supernatant and a precipitate. For example, the precipitate obtained from transformant JM 109/pCE 066 was suspended in a solution of 100 mM Tris.HCl (pH 8.0) and 0.1% Triton X-100, and the resultant suspension was subjected to ultrasonic treatment at a frequency of 20 KHz (600 W) for one minute, followed by centrifugation at 21,000.times.g for 15 minutes, thereby obtaining a precipitate. The precipitate was re-suspended in a solution of 100 mM Tris.HCl (pH 8.0) and 6 M urea, and then subjected to ultrasonic treatment followed by centrifugation.
The resultant supernatant was dialyzed against a solution of 10 mM phosphoric acid buffer (pH 7.5) and 6 M urea to thereby obtain an antigen solution. 20 ml of the antigen solution was passed through a column (21.5.times.250 mm) packed with hydroxyapatite, which had been equilibrated with the above-mentioned buffer, to cause the antigen to be adsorbed onto the packing material. The column was subjected to high speed liquid chromatography (HPLC) wherein elution was performed with the above-mentioned buffer having, added thereto, sodium chloride, the concentration of which was varied from 0 to 2 M with a linear concentration gradient, thereby obtaining a fraction containing an antigen. The obtained fraction was dialyzed against a solution of 50 mM carbonate buffer (pH 9.6) and 0.05% sodium dodecyl sulfate (SDS).
Further, the supernatant obtained by centrifugation (at 10,000 g for 15 minutes) of the lysate of transformant JM 109/pB-02-10 was treated with 35% saturated ammonium sulfate, and the obtained precipitate was dissolved in a solution of 50 mM Tris.HCl (pH 8.5) and 100 mM 2-mercaptoethanol. The resultant solution was dialyzed against the above-mentioned buffer. Subsequently, 100 ml of the dialysed solution was passed through a column (22.0.times.200 mm) packed with DEAE cellulose, which had been equilibrated with the above-mentioned buffer, to cause the antigen to be adsorbed onto the packing material. The column was subjected to high performance liquid chromatography wherein elution was performed with a solution of 50 mM Tris.HCl (pH 8.5) and 100 mM 2-mercaptoethanol having, added thereto, sodium chloride, the concentration of which was varied from 0 to 2 M with a linear concentration gradient, thereby pooling a fraction containing the antigen.
The fraction was dialyzed against a solution of 10 mM phosphate buffer (pH 6.8) and 100 mM 2-mercaptoethanol. The dialyzed solution was passed through the column of hydroxyapatite for high performance liquid chromatography, which had been equilibrated by the above-mentioned buffer, to cause the antigen to be adsorbed onto the packing material. The column was subjected to high speed liquid chromatography wherein elution was performed with phosphoric acid, the concentration of which was carried with a linear concentration gradient from 10 to 400 mM, thereby pooling a fraction containing the antigen. The resultant fraction was dialyzed against a solution of 50 mM carbonate buffer (pH 9.6) and 0.05% SDS.
The precipitate obtained by centrifugation of the lysate of transformant JM 109/pE-11-89 was suspended in 10 mM phosphate buffer (pH 5.5). The suspension was subjected to the above-mentioned ultrasonic treatment for one minute, and then subjected to centrifugation at 21,000.times.g for 15 minutes. The resultant precipitate was suspended in a solution of 100 mM carbonate buffer (pH 10.5), 500 mM sodium chloride and 10 mM EDTA. The resultant suspension was again subjected to the ultrasonic treatment for one minute, followed by centrifugation. The resultant supernatant was dialyzed against a solution of 30 mM phosphate buffer and 6 M urea. Subsequently, 20 ml of the dialyzed solution was passed through a CM cellulose column (22.times.200 mm) for high performance liquid chromatography (HPLC), which had been equilibrated with the same buffer as used for the above-mentioned dialysis, to thereby cause the antigen to be adsorbed onto the packing material. The column was subjected to high performance liquid chromatography wherein elution was performed with the above-mentioned buffer having, added thereto, sodium chloride, the concentration of which was varied from 0 to 1.5 M with a linear concentration gradient, obtaining a fraction containing the antigen. The fraction was dialyzed against a solution containing 50 mM carbonate buffer (pH 9.6) and 0.05% SDS, thereby obtaining a solution containing the antigen.
The antigens prepared above were used as an antigen for ELISA for the clinical diagnosis of infection with non-A, non-B hepatitis virus. The protein concentration of each of the above-mentioned purified antigens was adjusted to 1 .mu.g/ml, and put in each well of Microplate Immulone 600 (manufactured and sold by Greiner, Co., Ltd., Germany) in an amount of 100 ml for use in ELISA, which well was allowed to stand still at 4.degree. C. overnight. The contents of the individual wells were washed well three times with PBS-T buffer containing 10 mM phosphate buffer (pH 7.2), 0.8% sodium chloride and 0.05% Tween 20, and sample serum diluted with the PBS-T buffer was added in an amount of 100 .mu.l/well, followed by reaction at 37.degree. C. for one hour. The contents of the individual wells were washed three times with the PBS-T buffer, and a peroxidase-labeled anti-human IgG antibody (manufactured and sold by Cappel Co., Ltd., Germany) which had been diluted 8000-fold with PBS-T buffer containing 10% fetal calf serum was added in an amount of 100 .mu.l/well. The individual well contents were reacted at 37.degree. C. for one hour, and washed with the PBS-T buffer four times. A substrate coloring agent solution composed of 9 ml of 0.05 M citric acid-phosphate buffer and, contained therein, 0.5 .mu.g of o-phenylenediamine and 20 .mu.l of aqueous hydrogen peroxide, was added in an amount of 100 .mu.l/well. The plate was light shielded, and allowed to stand still at room temperature for 60 minutes. 75 .mu.l of 4 N sulfuric acid was added to each of the wells, and the absorbance at 490 nm was determined. The results are shown in Table 3. As apparent from the table, all of the antigens derived from the transformant specifically react with the serum from NANB hepatitis patient, thereby attesting to the usefulness in clinical diagnosis of the antigens produced by the transofrmants.
TABLE 3______________________________________Reactivity in ELISA between the purified antigens from various transformed Escherichia coli and the serum from NANB hepatitis patient origin of Serum from blood transfused antigen patient of hepatitis(transformed healthy Escherichia hepato- human coli) acute chronic cirrhosis hepatoma serum______________________________________JM109/pCE-066 2/3* 7/8 3/4 3/3 0/10 JM109/pB-02-10 2/3 8/8 4/4 3/3 0/10 JM109/pE-11-89 2/3 8/8 2/4 3/3 0/10______________________________________ *the number of positive samples/the number of samples examined
The same results as shown in Table 3 were also obtained by radioimmunoassay using the above-mentioned antigens. That is, a polystyrene ball of 1/4 inch in diameter (manufactured and sold by Pesel Co., Ltd., Germany) was put in 0.2 ml of each of the above-mentioned purified antigen solutions of 1 .mu.g/ml in concentration, and allowed to stand still at 4.degree. C. overnight. Then, the polystyrene ball was washed five times with the same PBS-T buffer as used in the above-mentioned ELISA, and a sample serum diluted 20 to 2500-fold with the PBS-T buffer was added in an amount of 200 .mu.l/ball. Reaction was performed at 37.degree. C. for 60 min. The polystyrene ball was washed five times with the PBS-T buffer, and .sup.125 I-labeled anti-human IgG antibody was added in an amount of 200 .mu.l/ball. Reaction was performed at 37.degree. C. for one hour and the ball was washed five times with the PBS-T buffer. The cpm of .sup.125 I bound to the polystyrene ball was measured, thereby obtaining the same results as shown in Table 3. Thus, the usefulness of the purified antigens obtained above in the clinical diagnosis of infection with NANB hepatitis virus, was demonstrated.
APPLICATION EXAMPLE 1
Assay of the reactivity of synthetic polypeptide
The antibody molecule reacts with a specific region structure known as "epitope" which exists on the antigen molecule, to thereby form a bonding therebetween. Such a specific region can be found in the hydrophilic region of the antigen molecule. The antigen polypeptide having such a specific region is believed to be useful for easily preparing a valuable clinical diagnostic reagent with high reaction specificity. The NANBV epitope is presumed from the hydrophilicity/hydrophobicity pattern of the amino acid sequence coded for by the NANBV genomic cDNA shown in FIGS. 2(1) to 2(16) Namely, polypeptides BKP-106-1, BKP-106-2, BKP-102-1 and BKP-147-1 were prepared, which were respectively comprised of amino acid residues coded for by nucleotide numbers 333 to 422 shown in FIG. 2(1), nucleotide numbers 474 to 563 shown in FIG. 2(1) through FIG. 2(2), nucleotide numbers 4485 to 4574 shown in FIG. 2(8), and nucleotide numbers 5544 to 5633 shown in FIG. 2(10) of SEQ ID NO:1. The concentration of each of the prepared polypeptides was adjusted to 1 .mu.g/ml, applied to a microplate for ELISA according to the same method as described in Step 12 to thereby form a solid phase, and examined with respect to the reactivity thereof with the serum from NANB hepatitis patient by the method of ELISA. The results are shown in Table 4. As apparent from the table, all of the prepared polypeptides specifically reacted with the serum from NANB hepatitis patient, thereby demonstrating the importance in clinical diagnosis of the particular regions of nucleotide sequences described above.
TABLE 4______________________________________Reactivity of synthetic polypeptides with the serum from NANB hepatitis patient synthetic serum from NANB hepatitis patient healthypolypeptides acute chronic human______________________________________BKP-106-1 2/5 5/5 0/5 BKP-106-2 2/5 5/5 0/5 BKP-102-1 3/5 5/5 0/5 BKP-147-1 2/5 5/5 0/5______________________________________
Moreover, presuming the epitopes of the envelop protein of NANBV, three types of proteins were prepared. That is, proteins coded for by nucleotide numbers 906 to 953 shown in FIG. 2(2), nucleotide numbers 1020 to 1046 shown in FIG. 2(2) and nucleotide numbers 1194 to 1232 shown in FIG. 2(2) through FIG. 2(3) of SEQ ID NO:1, were prepared. All of the thus prepared polypeptides correspond to the regions of the envelop where antigenic variation is believed to occur depending on the type of the NANBV strain, and the reactivity thereof in ELISA with the serum from a NANB hepatitis patient was confirmed. These attest to the importance and usefulness of the above-mentioned proteins in immunological survey, clinical diagnosis and vaccination.
APPLICATION EXAMPLE 2
Detection of NANBV nucleic acid according to PCT (Polymerase Chain Reaction) method
For preventing NANB hepatitis caused by blood transfusion, it is important to determine whether or not any NANBV infection exists in the blood supplied for transfusion. Further, for diagnosing hepatitis, it is extremely clinically important to study whether or not any NANBV infection exists in liver tissue. The NANBV cDNA of the present invention can be advantageously used for producing a primer for polymerase chain reaction (PCR) useful for detecting NANB hepatitis. That is, as described in Step 1, the purification of RNA and the preparation of cDNA were performed from 1 ml of serum. Likewise, cDNA was prepared from liver cells as described in Step 2. Subsequently, as described in Step 4 , PCT and electrophoresis were conducted. According to the customary procedure, whether or not the amplified cDNA was derived from NANBV, was investigated by Southern hybridization using .sup.32 P-labeled probe prepared from the cDNA derived from NANBV cDNA clone BK 108.
The results are shown in Table 5. From the table, it is apparent that the NANBV nucleic acid in serum can be detected and the serum infection with NANBV can be diagnosed by the use of the primer prepared from the nucleotide sequence of the NANBV cDNA obtained according to the present invention and the fragment of cloned NANBV cDNA as a probe.
TABLE 5______________________________________Detection of NANBV nucleic acid by PCR antibody against sample NANBV PCR______________________________________serum from chronic hepatitis patient NANB 1 + + 2 + + HBV carrier 1 - - 2 - -healthy human 1 - - 2 - -excised liver + from NANB hepatoma-1cancerous site + non-cancerous site +excised liver + from NANB hepatoma-2cancerous site + non-cancerous site +______________________________________
__________________________________________________________________________# SEQUENCE LISTING - - - - (1) GENERAL INFORMATION: - - (iii) NUMBER OF SEQUENCES: 50 - - - - (2) INFORMATION FOR SEQ ID NO:1: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9416 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 333..9362 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1: - - CGATTGGGGG CGACACTCCA CCATAGATCA CTCCCCTGTG AGGAACTACT GT -#CTTCACGC 60 - - AGAAAGCGTC TAGCCATGGC GTTAGTATGA GTGTCGTGCA GCCTCCAGGA CC -#CCCCCTCC 120 - - CGGGAGAGCC ATAGTGGTCT GCGGAACCGG TGAGTACACC GGAATTGCCA GG -#ACGACCGG 180 - - GTCCTTTCTT GGATCAACCC GCTCAATGCC TGGAGATTTG GGCGTGCCCC CG -#CGAGACTG 240 - - CTAGCCGAGT AGTGTTGGGT CGCGAAAGGC CTTGTGGTAC TGCCTGATAG GG -#TGCTTGCG 300 - - AGTGCCCCGG GAGGTCTCGT AGACCGTGCA CC ATG AGC ACG AAT - # CCT AAACCT 353 - # - #Met Ser Thr Asn Pro Lys Pro - # - # 1 5 - - CAA AGA AAA ACC AAA CGT AAC ACC AAC CGC CG - #C CCA CAG GAC GTC AAG 401 Gln Arg Lys Thr Lys Arg Asn Thr Asn Arg Ar - #g Pro Gln Asp Val Lys 10 - # 15 - # 20 - - TTC CCG GGC GGT GGT CAG ATC GTT GGT GGA GT - #T TAC CTG TTG CCG CGC 449 Phe Pro Gly Gly Gly Gln Ile Val Gly Gly Va - #l Tyr Leu Leu Pro Arg 25 - # 30 - # 35 - - AGG GGC CCC AGG TTG GGT GTG CGC GCG CCC AG - #G AAG ACT TCC GAG CGG 497 Arg Gly Pro Arg Leu Gly Val Arg Ala Pro Ar - #g Lys Thr Ser Glu Arg 40 - # 45 - # 50 - # 55 - - TCG CAA CCT CGT GGA AGG CGA CAA CCT ATC CC - #C AAG GCT CGC CGG CCC 545 Ser Gln Pro Arg Gly Arg Arg Gln Pro Ile Pr - #o Lys Ala Arg Arg Pro 60 - # 65 - # 70 - - GAG GGC AGG ACC TGG GCT CAG CCC GGG TAC CC - #T TGG CCT CTC TAT GGC 593 Glu Gly Arg Thr Trp Ala Gln Pro Gly Tyr Pr - #o Trp Pro Leu Tyr Gly 75 - # 80 - # 85 - - AAT GAG GGC TTA GGG TGG GCA GGA TGG CTC CT - #G TCA CCC CGC GGC TCC 641 Asn Glu Gly Leu Gly Trp Ala Gly Trp Leu Le - #u Ser Pro Arg Gly Ser 90 - # 95 - # 100 - - CGG CCT AGT TGG GGC CCC ACG GAC CCC CGG CG - #T AGG TCG CGT AAT TTG 689 Arg Pro Ser Trp Gly Pro Thr Asp Pro Arg Ar - #g Arg Ser Arg Asn Leu 105 - # 110 - # 115 - - GGT AAG GTC ATC GAT ACC CTC ACA TGC GGC TT - #C GCC GAT CTC ATG GGG 737 Gly Lys Val Ile Asp Thr Leu Thr Cys Gly Ph - #e Ala Asp Leu Met Gly 120 1 - #25 1 - #30 1 -#35 - - TAC ATT CCG CTC GTC GGC GCC CCC CTG GGG GG - #C GCT GCC AGG GCCCTG 785 Tyr Ile Pro Leu Val Gly Ala Pro Leu Gly Gl - #y Ala Ala Arg Ala Leu 140 - # 145 - # 150 - - GCA CAT GGT GTC CGG GTT CTG GAG GAC GGC GT - #G AAC TAT GCA ACA GGG 833 Ala His Gly Val Arg Val Leu Glu Asp Gly Va - #l Asn Tyr Ala Thr Gly 155 - # 160 - # 165 - - AAT CTG CCC GGT TGC TCT TTT TCT ATC TTC CT - #C TTG GCT CTG CTG TCC 881 Asn Leu Pro Gly Cys Ser Phe Ser Ile Phe Le - #u Leu Ala Leu Leu Ser 170 - # 175 - # 180 - - TGC CTG ACC ACC CCA GCT TCC GCT TAC GAA GT - #G CAC AAC GTG TCC GGG 929 Cys Leu Thr Thr Pro Ala Ser Ala Tyr Glu Va - #l His Asn Val Ser Gly 185 - # 190 - # 195 - - ATA TAT CAT GTC ACG AAC GAC TGC TCC AAC GC - #A AGC ATT GTG TAT GAG 977 Ile Tyr His Val Thr Asn Asp Cys Ser Asn Al - #a Ser Ile Val Tyr Glu 200 2 - #05 2 - #10 2 -#15 - - GCA GCG GAC TTG ATC ATG CAT ACT CCT GGG TG - #C GTG CCC TGC GTTCGG 1025 Ala Ala Asp Leu Ile Met His Thr Pro Gly Cy - #s Val Pro Cys Val Arg 220 - # 225 - # 230 - - GAA GGC AAC TCC TCC CGC TGC TGG GTA GCG CT - #C ACT CCC ACG CTC GCA 1073 Glu Gly Asn Ser Ser Arg Cys Trp Val Ala Le - #u Thr Pro Thr Leu Ala 235 - # 240 - # 245 - - GCC AGG AAC GTC ACC ATC CCC ACC ACG ACG AT - #A CGA CGC CAC GTC GAT 1121 Ala Arg Asn Val Thr Ile Pro Thr Thr Thr Il - #e Arg Arg His Val Asp 250 - # 255 - # 260 - - CTG CTC GTT GGG GCG GCT GCT TTC TGT TCC GC - #T ATG TAC GTG GGG GAC 1169 Leu Leu Val Gly Ala Ala Ala Phe Cys Ser Al - #a Met Tyr Val Gly Asp 265 - # 270 - # 275 - - CTC TGC GGA TCT GTT TTC CTC GTC TCT CAG CT - #G TTC ACC TTC TCG CCT 1217 Leu Cys Gly Ser Val Phe Leu Val Ser Gln Le - #u Phe Thr Phe Ser Pro 280 2 - #85 2 - #90 2 -#95 - - CGC CGG CAT GTG ACA TTA CAG GAC TGT AAC TG - #C TCA ATT TAT CCCGGC 1265 Arg Arg His Val Thr Leu Gln Asp Cys Asn Cy - #s Ser Ile Tyr Pro Gly 300 - # 305 - # 310 - - CAT GTG TCG GGT CAC CGT ATG GCT TGG GAC AT - #G ATG ATG AAC TGG TCG 1313 His Val Ser Gly His Arg Met Ala Trp Asp Me - #t Met Met Asn Trp Ser 315 - # 320 - # 325 - - CCC ACA ACA GCC CTA GTG GTG TCG CAG TTA CT - #C CGG ATC CCA CAA GCC 1361 Pro Thr Thr Ala Leu Val Val Ser Gln Leu Le - #u Arg Ile Pro Gln Ala 330 - # 335 - # 340 - - GTC GTG GAC ATG GTG GCG GGG GCC CAC TGG GG - #A GTC CTG GCG GGC CTT 1409 Val Val Asp Met Val Ala Gly Ala His Trp Gl - #y Val Leu Ala Gly Leu 345 - # 350 - # 355 - - GCC TAC TAT TCC ATG GCG GGG AAC TGG GCT AA - #G GTT CTG ATT GTG ATG 1457 Ala Tyr Tyr Ser Met Ala Gly Asn Trp Ala Ly - #s Val Leu Ile Val Met 360 3 - #65 3 - #70 3 -#75 - - CTA CTT TTT GCT GGC GTT GAC GGG GAT ACC CA - #C GTG ACA GGG GGGGCG 1505 Leu Leu Phe Ala Gly Val Asp Gly Asp Thr Hi - #s Val Thr Gly Gly Ala 380 - # 385 - # 390 - - CAA GCC AAA ACC ACC AAC AGG CTC GTG TCC AT - #G TTC GCA AGT GGG CCG 1553 Gln Ala Lys Thr Thr Asn Arg Leu Val Ser Me - #t Phe Ala Ser Gly Pro 395 - # 400 - # 405 - - TCT CAG AAA ATC CAG CTT ATA AAC ACC AAT GG - #G AGT TGG CAC ATC AAC 1601 Ser Gln Lys Ile Gln Leu Ile Asn Thr Asn Gl - #y Ser Trp His Ile Asn 410 - # 415 - # 420 - - AGG ACT GCC CTG AAC TGC AAT GAC TCT CTC CA - #G ACT GGG TTT CTT GCC 1649 Arg Thr Ala Leu Asn Cys Asn Asp Ser Leu Gl - #n Thr Gly Phe Leu Ala 425 - # 430 - # 435 - - GCG CTG TTC TAC ACA CAT AGT TTC AAC TCG TC - #C GGG TGC CCA GAG CGC 1697 Ala Leu Phe Tyr Thr His Ser Phe Asn Ser Se - #r Gly Cys Pro Glu Arg 440 4 - #45 4 - #50 4 -#55 - - ATG GCC CAG TGC CGC ACC ATT GAC AAG TTC GA - #C CAG GGA TGG GGTCCC 1745 Met Ala Gln Cys Arg Thr Ile Asp Lys Phe As - #p Gln Gly Trp Gly Pro 460 - # 465 - # 470 - - ATT ACT TAT GCT GAG TCT AGC AGA TCA GAC CA - #G AGG CCA TAT TGC TGG 1793 Ile Thr Tyr Ala Glu Ser Ser Arg Ser Asp Gl - #n Arg Pro Tyr Cys Trp 475 - # 480 - # 485 - - CAC TAC CCA CCT CCA CAA TGT ACC ATC GTA CC - #T GCG TCG GAG GTG TGC 1841 His Tyr Pro Pro Pro Gln Cys Thr Ile Val Pr - #o Ala Ser Glu Val Cys 490 - # 495 - # 500 - - GGC CCA GTG TAC TGC TTC ACC CCA AGC CCT GT - #C GTC GTG GGG ACG ACC 1889 Gly Pro Val Tyr Cys Phe Thr Pro Ser Pro Va - #l Val Val Gly Thr Thr 505 - # 510 - # 515 - - GAT CGT TTC GGT GTC CCT ACG TAT AGA TGG GG - #G GAG AAC GAG ACT GAC 1937 Asp Arg Phe Gly Val Pro Thr Tyr Arg Trp Gl - #y Glu Asn Glu Thr Asp 520 5 - #25 5 - #30 5 -#35 - - GTG CTG CTG CTC AAC AAC ACG CGG CCG CCG CA - #A GGC AAC TGG TTCGGC 1985 Val Leu Leu Leu Asn Asn Thr Arg Pro Pro Gl - #n Gly Asn Trp Phe Gly 540 - # 545 - # 550 - - TGC ACA TGG ATG AAT AGC ACC GGG TTC ACC AA - #G ACA TGT GGG GGG CCC 2033 Cys Thr Trp Met Asn Ser Thr Gly Phe Thr Ly - #s Thr Cys Gly Gly Pro 555 - # 560 - # 565 - - CCG TGT AAC ATC GGG GGG GTC GGC AAC AAC AC - #C CTG ACC TGC CCC ACG 2081 Pro Cys Asn Ile Gly Gly Val Gly Asn Asn Th - #r Leu Thr Cys Pro Thr 570 - # 575 - # 580 - - GAC TGC TTC CGG AAG CAC CCC GAG GCT ACC TA - #C ACA AAA TGT GGT TCG 2129 Asp Cys Phe Arg Lys His Pro Glu Ala Thr Ty - #r Thr Lys Cys Gly Ser 585 - # 590 - # 595 - - GGG CCT TGG CTG ACA CCT AGG TGC ATG GTT GA - #C TAT CCA TAC AGG CTC 2177 Gly Pro Trp Leu Thr Pro Arg Cys Met Val As - #p Tyr Pro Tyr Arg Leu 600 6 - #05 6 - #10 6 -#15 - - TGG CAT TAC CCC TGC ACT GTT AAC TTT ACC AT - #C TTC AAG GTT AGGATG 2225 Trp His Tyr Pro Cys Thr Val Asn Phe Thr Il - #e Phe Lys Val Arg Met 620 - # 625 - # 630 - - TAT GTG GGG GGG GTG GAG CAC AGG CTC AAT GC - #T GCA TGC AAT TGG ACC 2273 Tyr Val Gly Gly Val Glu His Arg Leu Asn Al - #a Ala Cys Asn Trp Thr 635 - # 640 - # 645 - - CGA GGA GAG CGT TGT GAC TTG GAG GAC AGG GA - #T AGG CCG GAG CTC AGC 2321 Arg Gly Glu Arg Cys Asp Leu Glu Asp Arg As - #p Arg Pro Glu Leu Ser 650 - # 655 - # 660 - - CCG CTG CTG CTG TCT ACA ACA GAG TGG CAG GT - #A CTG CCC TGT TCC TTC 2369 Pro Leu Leu Leu Ser Thr Thr Glu Trp Gln Va - #l Leu Pro Cys Ser Phe 665 - # 670 - # 675 - - ACC ACC CTA CCA GCT CTG TCC ACT GGC TTG AT - #T CAC CTC CAT CAG AAC 2417 Thr Thr Leu Pro Ala Leu Ser Thr Gly Leu Il - #e His Leu His Gln Asn 680 6 - #85 6 - #90 6 -#95 - - ATC GTG GAC GTG CAA TAC CTA TAC GGT ATA GG - #G TCA GCG GTT GTCTCC 2465 Ile Val Asp Val Gln Tyr Leu Tyr Gly Ile Gl - #y Ser Ala Val Val Ser 700 - # 705 - # 710 - - TTT GCA ATC AAA TGG GAG TAT GTC CTG TTG CT - #T TTC CTT CTC CTA GCG 2513 Phe Ala Ile Lys Trp Glu Tyr Val Leu Leu Le - #u Phe Leu Leu Leu Ala 715 - # 720 - # 725 - - GAC GCA CGT GTC TGT GCC TGC TTG TGG ATG AT - #G CTG CTG ATA GCC CAG 2561 Asp Ala Arg Val Cys Ala Cys Leu Trp Met Me - #t Leu Leu Ile Ala Gln 730 - # 735 - # 740 - - GCC GAG GCC GCC TTG GAG AAC CTG GTG GTC CT - #C AAT TCG GCG TCT GTG 2609 Ala Glu Ala Ala Leu Glu Asn Leu Val Val Le - #u Asn Ser Ala Ser Val 745 - # 750 - # 755 - - GCC GGC GCA CAT GGC ATC CTC TCC TTC CTT GT - #G TTC TTC TGT GCC GCC 2657 Ala Gly Ala His Gly Ile Leu Ser Phe Leu Va - #l Phe Phe Cys Ala Ala 760 7 - #65 7 - #70 7 -#75 - - TGG TAC ATC AAA GGC AGG CTG GTC CCT GGG GC - #G ACA TAT GCT CTTTAT 2705 Trp Tyr Ile Lys Gly Arg Leu Val Pro Gly Al - #a Thr Tyr Ala Leu Tyr 780 - # 785 - # 790 - - GGC GTG TGG CCG CTG CTC CTG CTC TTG CTG GC - #A TTA CCA CCG CGA GCT 2753 Gly Val Trp Pro Leu Leu Leu Leu Leu Leu Al - #a Leu Pro Pro Arg Ala 795 - # 800 - # 805 - - TAC GCC ATG GAC CGG GAG ATG GCT GCA TCG TG - #C GGA GGC GCG GTT TTT 2801 Tyr Ala Met Asp Arg Glu Met Ala Ala Ser Cy - #s Gly Gly Ala Val Phe 810 - # 815 - # 820 - - GTG GGT CTG GTA CTC CTG ACT TTG TCA CCA TA - #C TAC AAG GTG TTC CTC 2849 Val Gly Leu Val Leu Leu Thr Leu Ser Pro Ty - #r Tyr Lys Val Phe Leu 825 - # 830 - # 835 - - GCT AGG CTC ATA TGG TGG TTA CAA TAT TTT AC - #C ACC AGA GCC GAG GCG 2897 Ala Arg Leu Ile Trp Trp Leu Gln Tyr Phe Th - #r Thr Arg Ala Glu Ala 840 8 - #45 8 - #50 8 -#55 - - GAC TTA CAT GTG TGG ATC CCC CCC CTC AAC GC - #T CGG GGA GGC CGCGAT 2945 Asp Leu His Val Trp Ile Pro Pro Leu Asn Al - #a Arg Gly Gly Arg Asp 860 - # 865 - # 870 - - GCC ATC ATC CTC CTC ATG TGC GCA GTC CAT CC - #A GAG CTA ATC TTT GAC 2993 Ala Ile Ile Leu Leu Met Cys Ala Val His Pr - #o Glu Leu Ile Phe Asp 875 - # 880 - # 885 - - ATC ACC AAA CTT CTA ATT GCC ATA CTC GGT CC - #G CTC ATG GTG CTC CAA 3041 Ile Thr Lys Leu Leu Ile Ala Ile Leu Gly Pr - #o Leu Met Val Leu Gln 890 - # 895 - # 900 - - GCT GGC ATA ACC AGA GTG CCG TAC TTC GTG CG - #C GCT CAA GGG CTC ATT 3089 Ala Gly Ile Thr Arg Val Pro Tyr Phe Val Ar - #g Ala Gln Gly Leu Ile 905 - # 910 - # 915 - - CAT GCA TGC ATG TTA GTG CGG AAG GTC GCT GG - #G GGT CAT TAT GTC CAA 3137 His Ala Cys Met Leu Val Arg Lys Val Ala Gl - #y Gly His Tyr Val Gln 920 9 - #25 9 - #30 9 -#35 - - ATG GCC TTC ATG AAG CTG GGC GCG CTG ACA GG - #C ACG TAC ATT TACAAC 3185 Met Ala Phe Met Lys Leu Gly Ala Leu Thr Gl - #y Thr Tyr Ile Tyr Asn 940 - # 945 - # 950 - - CAT CTT ACC CCG CTA CGG GAT TGG CCA CGC GC - #G GGC CTA CGA GAC CTT 3233 His Leu Thr Pro Leu Arg Asp Trp Pro Arg Al - #a Gly Leu Arg Asp Leu 955 - # 960 - # 965 - - GCG GTG GCA GTG GAG CCC GTC GTC TTC TCC GA - #C ATG GAG ACC AAG ATC 3281 Ala Val Ala Val Glu Pro Val Val Phe Ser As - #p Met Glu Thr Lys Ile 970 - # 975 - # 980 - - ATC ACC TGG GGA GCA GAC ACC GCG GCG TGT GG - #G GAC ATC ATC TTG GGT 3329 Ile Thr Trp Gly Ala Asp Thr Ala Ala Cys Gl - #y Asp Ile Ile Leu Gly 985 - # 990 - # 995 - - CTG CCC GTC TCC GCC CGA AGG GGA AAG GAG AT - #A CTC CTG GGC CCG GCC 3377 Leu Pro Val Ser Ala Arg Arg Gly Lys Glu Il - #e Leu Leu Gly Pro Ala 1000 1005 - # 1010 - # 1015 - - GAT AGT CTT GAA GGG CGG GGG TTG CGA CTC CT - #C GCG CCC ATC ACG GCC 3425 Asp Ser Leu Glu Gly Arg Gly Leu Arg Leu Le - #u Ala Pro Ile Thr Ala 1020 - # 1025 - # 1030 - - TAC TCC CAA CAG ACG CGG GGC CTA CTT GGT TG - #C ATC ATC ACT AGC CTT 3473 Tyr Ser Gln Gln Thr Arg Gly Leu Leu Gly Cy - #s Ile Ile Thr Ser Leu 1035 - # 1040 - # 1045 - - ACA GGC CGG GAC AAG AAC CAG GTC GAG GGA GA - #G GTT CAG GTG GTT TCC 3521 Thr Gly Arg Asp Lys Asn Gln Val Glu Gly Gl - #u Val Gln Val Val Ser 1050 - # 1055 - # 1060 - - ACC GCA ACA CAA TCC TTC CTG GCG ACC TGC GT - #C AAC GGC GTG TGT TGG 3569 Thr Ala Thr Gln Ser Phe Leu Ala Thr Cys Va - #l Asn Gly Val Cys Trp 1065 - # 1070 - # 1075 - - ACC GTT TAC CAT GGT GCT GGC TCA AAG ACC TT - #A GCC GCG CCA AAG GGG 3617 Thr Val Tyr His Gly Ala Gly Ser Lys Thr Le - #u Ala Ala Pro Lys Gly 1080 1085 - # 1090 - # 1095 - - CCA ATC ACC CAG ATG TAC ACT AAT GTG GAC CA - #G GAC CTC GTC GGC TGG 3665 Pro Ile Thr Gln Met Tyr Thr Asn Val Asp Gl - #n Asp Leu Val Gly Trp 1100 - # 1105 - # 1110 - - CCC AAG CCC CCC GGG GCG CGT TCC TTG ACA CC - #A TGC ACC TGT GGC AGC 3713 Pro Lys Pro Pro Gly Ala Arg Ser Leu Thr Pr - #o Cys Thr Cys Gly Ser 1115 - # 1120 - # 1125 - - TCA GAC CTT TAC TTG GTC ACG AGA CAT GCT GA - #C GTC ATT CCG GTG CGC 3761 Ser Asp Leu Tyr Leu Val Thr Arg His Ala As - #p Val Ile Pro Val Arg 1130 - # 1135 - # 1140 - - CGG CGG GGC GAC AGT AGG GGG AGC CTG CTC TC - #C CCC AGG CCT GTC TCC 3809 Arg Arg Gly Asp Ser Arg Gly Ser Leu Leu Se - #r Pro Arg Pro Val Ser 1145 - # 1150 - # 1155 - - TAC TTG AAG GGC TCT TCG GGT GGT CCA CTG CT - #C TGC CCC TTC GGG CAC 3857 Tyr Leu Lys Gly Ser Ser Gly Gly Pro Leu Le - #u Cys Pro Phe Gly His 1160 1165 - # 1170 - # 1175 - - GCT GTG GGC ATC TTC CGG GCT GCC GTA TGC AC - #C CGG GGG GTT GCG AAG 3905 Ala Val Gly Ile Phe Arg Ala Ala Val Cys Th - #r Arg Gly Val Ala Lys 1180 - # 1185 - # 1190 - - GCG GTG GAC TTT GTG CCC GTA GAG TCC ATG GA - #A ACT ACT ATG CGG TCT 3953 Ala Val Asp Phe Val Pro Val Glu Ser Met Gl - #u Thr Thr Met Arg Ser 1195 - # 1200 - # 1205 - - CCG GTC TTC ACG GAC AAC TCA TCC CCC CCG GC - #C GTA CCG CAG TCA TTT 4001 Pro Val Phe Thr Asp Asn Ser Ser Pro Pro Al - #a Val Pro Gln Ser Phe 1210 - # 1215 - # 1220 - - CAA GTG GCC CAC CTA CAC GCT CCC ACT GGC AG - #C GGC AAG AGT ACT AAA 4049 Gln Val Ala His Leu His Ala Pro Thr Gly Se - #r Gly Lys Ser Thr Lys 1225 - # 1230 - # 1235 - - GTG CCG GCT GCA TAT GCA GCC CAA GGG TAC AA - #G GTG CTC GTC CTC AAT 4097 Val Pro Ala Ala Tyr Ala Ala Gln Gly Tyr Ly - #s Val Leu Val Leu Asn 1240 1245 - # 1250 - # 1255 - - CCG TCC GTT GCC GCT ACC TTA GGG TTT GGG GC - #G TAT ATG TCT AAG GCA 4145 Pro Ser Val Ala Ala Thr Leu Gly Phe Gly Al - #a Tyr Met Ser Lys Ala 1260 - # 1265 - # 1270 - - CAC GGT ATT GAC CCC AAC ATC AGA ACT GGG GT - #A AGG ACC ATT ACC ACA 4193 His Gly Ile Asp Pro Asn Ile Arg Thr Gly Va - #l Arg Thr Ile Thr Thr 1275 - # 1280 - # 1285 - - GGC GCC CCC GTC ACA TAC TCT ACC TAT GGC AA - #G TTT CTT GCC GAT GGT 4241 Gly Ala Pro Val Thr Tyr Ser Thr Tyr Gly Ly - #s Phe Leu Ala Asp Gly 1290 - # 1295 - # 1300 - - GGT TGC TCT GGG GGC GCT TAT GAC ATC ATA AT - #A TGT GAT GAG TGC CAT 4289 Gly Cys Ser Gly Gly Ala Tyr Asp Ile Ile Il - #e Cys Asp Glu Cys His 1305 - # 1310 - # 1315 - - TCA ACT GAC TCG ACT ACA ATC TTG GGC ATC GG - #C ACA GTC CTG GAC CAA 4337 Ser Thr Asp Ser Thr Thr Ile Leu Gly Ile Gl - #y Thr Val Leu Asp Gln 1320 1325 - # 1330 - # 1335 - - GCG GAG ACG GCT GGA GCG CGG CTT GTC GTG CT - #C GCC ACC GCT ACG CCT 4385 Ala Glu Thr Ala Gly Ala Arg Leu Val Val Le - #u Ala Thr Ala Thr Pro 1340 - # 1345 - # 1350 - - CCG GGA TCG GTC ACC GTG CCA CAC CCA AAC AT - #C GAG GAG GTG GCC CTG 4433 Pro Gly Ser Val Thr Val Pro His Pro Asn Il - #e Glu Glu Val Ala Leu 1355 - # 1360 - # 1365 - - TCT AAT ACT GGA GAG ATC CCC TTC TAT GGC AA - #A GCC ATC CCC ATT GAA 4481 Ser Asn Thr Gly Glu Ile Pro Phe Tyr Gly Ly - #s Ala Ile Pro Ile Glu 1370 - # 1375 - # 1380 - - GCC ATC AGG GGG GGA AGG CAT CTC ATT TTC TG - #T CAT TCC AAG AAG AAG 4529 Ala Ile Arg Gly Gly Arg His Leu Ile Phe Cy - #s His Ser Lys Lys Lys 1385 - # 1390 - # 1395 - - TGC GAC GAG CTC GCC GCA AAG CTG TCA GGC CT - #C GGA ATC AAC GCT GTG 4577 Cys Asp Glu Leu Ala Ala Lys Leu Ser Gly Le - #u Gly Ile Asn Ala Val 1400 1405 - # 1410 - # 1415 - - GCG TAT TAC CGG GGG CTC GAT GTG TCC GTC AT - #A CCA ACT ATC GGA GAC 4625 Ala Tyr Tyr Arg Gly Leu Asp Val Ser Val Il - #e Pro Thr Ile Gly Asp 1420 - # 1425 - # 1430 - - GTC GTT GTC GTG GCA ACA GAC GCT CTG ATG AC - #G GGC TAT ACG GGC GAC 4673 Val Val Val Val Ala Thr Asp Ala Leu Met Th - #r Gly Tyr Thr Gly Asp 1435 - # 1440 - # 1445 - - TTT GAC TCA GTG ATC GAC TGT AAC ACA TGT GT - #C ACC CAG ACA GTC GAC 4721 Phe Asp Ser Val Ile Asp Cys Asn Thr Cys Va - #l Thr Gln Thr Val Asp 1450 - # 1455 - # 1460 - - TTC AGC TTG GAT CCC ACC TTC ACC ATT GAG AC - #G ACG ACC GTG CCT CAA 4769 Phe Ser Leu Asp Pro Thr Phe Thr Ile Glu Th - #r Thr Thr Val Pro Gln 1465 - # 1470 - # 1475 - - GAC GCA GTG TCG CGC TCG CAG CGG CGG GGT AG - #G ACT GGC AGG GGT AGG 4817 Asp Ala Val Ser Arg Ser Gln Arg Arg Gly Ar - #g Thr Gly Arg Gly Arg 1480 1485 - # 1490 - # 1495 - - AGA GGC ATC TAC AGG TTT GTG ACT CCG GGA GA - #A CGG CCC TCG GGC ATG 4865 Arg Gly Ile Tyr Arg Phe Val Thr Pro Gly Gl - #u Arg Pro Ser Gly Met 1500 - # 1505 - # 1510 - - TTC GAT TCC TCG GTC CTG TGT GAG TGC TAT GA - #C GCG GGC TGT GCT TGG 4913 Phe Asp Ser Ser Val Leu Cys Glu Cys Tyr As - #p Ala Gly Cys Ala Trp 1515 - # 1520 - # 1525 - - TAC GAG CTC ACC CCG GCC GAG ACC TCG GTT AG - #G TTG CGG GCC TAC CTG 4961 Tyr Glu Leu Thr Pro Ala Glu Thr Ser Val Ar - #g Leu Arg Ala Tyr Leu 1530 - # 1535 - # 1540 - - AAC ACA CCA GGG TTG CCC GTT TGC CAG GAC CA - #C CTG GAG TTC TGG GAG 5009 Asn Thr Pro Gly Leu Pro Val Cys Gln Asp Hi - #s Leu Glu Phe Trp Glu 1545 - # 1550 - # 1555 - - AGT GTC TTC ACA GGC CTC ACC CAT ATA GAT GC - #A CAC TTC TTG TCC CAG 5057 Ser Val Phe Thr Gly Leu Thr His Ile Asp Al - #a His Phe Leu Ser Gln 1560 1565 - # 1570 - # 1575 - - ACC AAG CAG GCA GGA GAC AAC TTC CCC TAC CT - #G GTA GCA TAC CAA GCC 5105 Thr Lys Gln Ala Gly Asp Asn Phe Pro Tyr Le - #u Val Ala Tyr Gln Ala 1580 - # 1585 - # 1590 - - ACG GTG TGC GCC AGG GCT CAG GCC CCA CCT CC - #A TCA TGG GAT CAA ATG 5153 Thr Val Cys Ala Arg Ala Gln Ala Pro Pro Pr - #o Ser Trp Asp Gln Met 1595 - # 1600 - # 1605 - - TGG AAG TGT CTC ATA CGG CTG AAA CCT ACG CT - #G CAC GGG CCA ACA CCC 5201 Trp Lys Cys Leu Ile Arg Leu Lys Pro Thr Le - #u His Gly Pro Thr Pro 1610 - # 1615 - # 1620 - - TTG CTG TAC AGG CTG GGA GCC GTC CAG AAT GA - #G GTC ACC CTC ACC CAC 5249 Leu Leu Tyr Arg Leu Gly Ala Val Gln Asn Gl - #u Val Thr Leu Thr His 1625 - # 1630 - # 1635 - - CCC ATA ACC AAA TAC ATC ATG GCA TGC ATG TC - #G GCT GAC CTG GAG GTC 5297 Pro Ile Thr Lys Tyr Ile Met Ala Cys Met Se - #r Ala Asp Leu Glu Val 1640 1645 - # 1650 - # 1655 - - GTC ACT AGC ACC TGG GTG CTG GTG GGC GGA GT - #C CTT GCA GCT CTG GCC 5345 Val Thr Ser Thr Trp Val Leu Val Gly Gly Va - #l Leu Ala Ala Leu Ala 1660 - # 1665 - # 1670 - - GCG TAT TGC CTG ACA ACA GGC AGT GTG GTC AT - #T GTG GGT AGG ATT ATC 5393 Ala Tyr Cys Leu Thr Thr Gly Ser Val Val Il - #e Val Gly Arg Ile Ile 1675 - # 1680 - # 1685 - - TTG TCC GGG AGG CCG GCC ATT GTT CCC GAC AG - #G GAG CTT CTC TAC CAG 5441 Leu Ser Gly Arg Pro Ala Ile Val Pro Asp Ar - #g Glu Leu Leu Tyr Gln 1690 - # 1695 - # 1700 - - GAG TTC GAT GAA ATG GAA GAG TGC GCC TCG CA - #C CTC CCT TAC ATC GAG 5489 Glu Phe Asp Glu Met Glu Glu Cys Ala Ser Hi - #s Leu Pro Tyr Ile Glu 1705 - # 1710 - # 1715 - - CAG GGA ATG CAG CTC GCC GAG CAA TTC AAG CA - #G AAA GCG CTC GGG TTA 5537 Gln Gly Met Gln Leu Ala Glu Gln Phe Lys Gl - #n Lys Ala Leu Gly Leu 1720 1725 - # 1730 - # 1735 - - CTG CAA ACA GCC ACC AAA CAA GCG GAG GCT GC - #T GCT CCC GTG GTG GAG 5585 Leu Gln Thr Ala Thr Lys Gln Ala Glu Ala Al - #a Ala Pro Val Val Glu 1740 - # 1745 - # 1750 - - TCC AAG TGG CGA GCC CTT GAG ACA TTC TGG GC - #G AAG CAC ATG TGG AAT 5633 Ser Lys Trp Arg Ala Leu Glu Thr Phe Trp Al - #a Lys His Met Trp Asn 1755 - # 1760 - # 1765 - - TTC ATC AGC GGG ATA CAG TAC TTA GCA GGC TT - #A TCC ACT CTG CCT GGG 5681 Phe Ile Ser Gly Ile Gln Tyr Leu Ala Gly Le - #u Ser Thr Leu Pro Gly 1770 - # 1775 - # 1780 - - AAC CCC GCA ATA GCA TCA TTG ATG GCA TTC AC - #A GCC TCT ATC ACC AGC 5729 Asn Pro Ala Ile Ala Ser Leu Met Ala Phe Th - #r Ala Ser Ile Thr Ser 1785 - # 1790 - # 1795 - - CCG CTC ACC ACC CAA AGT ACC CTC CTG TTT AA - #C ATC TTG GGG GGG TGG 5777 Pro Leu Thr Thr Gln Ser Thr Leu Leu Phe As - #n Ile Leu Gly Gly Trp 1800 1805 - # 1810 - # 1815 - - GTG GCT GCC CAA CTC GCC CCC CCC AGC GCC GC - #T TCG GCT TTC GTG GGC 5825 Val Ala Ala Gln Leu Ala Pro Pro Ser Ala Al - #a Ser Ala Phe Val Gly 1820 - # 1825 - # 1830 - - GCC GGC ATC GCC GGT GCG GCT GTT GGC AGC AT - #A GGC CTT GGG AAG GTG 5873 Ala Gly Ile Ala Gly Ala Ala Val Gly Ser Il - #e Gly Leu Gly Lys Val 1835 - # 1840 - # 1845 - - CTT GTG GAC ATT CTG GCG GGT TAT GGA GCA GG - #A GTG GCC GGC GCG CTC 5921 Leu Val Asp Ile Leu Ala Gly Tyr Gly Ala Gl - #y Val Ala Gly Ala Leu 1850 - # 1855 - # 1860 - - GTG GCC TTT AAG GTC ATG AGC GGC GAG ATG CC - #C TCC ACC GAG GAC CTG 5969 Val Ala Phe Lys Val Met Ser Gly Glu Met Pr - #o Ser Thr Glu Asp Leu 1865 - # 1870 - # 1875 - - GTC AAT CTA CTT CCT GCC ATC CTC TCT CCT GG - #C GCC CTG GTC GTC GGG 6017 Val Asn Leu Leu Pro Ala Ile Leu Ser Pro Gl - #y Ala Leu Val Val Gly 1880 1885 - # 1890 - # 1895 - - GTC GTG TGT GCA GCA ATA CTG CGT CGA CAC GT - #G GGT CCG GGA GAG GGG 6065 Val Val Cys Ala Ala Ile Leu Arg Arg His Va - #l Gly Pro Gly Glu Gly 1900 - # 1905 - # 1910 - - GCT GTG CAG TGG ATG AAC CGG CTG ATA GCG TT - #C GCC TCG CGG GGT AAT 6113 Ala Val Gln Trp Met Asn Arg Leu Ile Ala Ph - #e Ala Ser Arg Gly Asn 1915 - # 1920 - # 1925 - - CAT GTT TCC CCC ACG CAC TAT GTG CCT GAG AG - #C GAC GCC GCA GCG CGT 6161 His Val Ser Pro Thr His Tyr Val Pro Glu Se - #r Asp Ala Ala Ala Arg 1930 - # 1935 - # 1940 - - GTT ACT CAG ATC CTC TCC AGC CTT ACC ATC AC - #T CAG CTG CTG AAA AGG 6209 Val Thr Gln Ile Leu Ser Ser Leu Thr Ile Th - #r Gln Leu Leu Lys Arg 1945 - # 1950 - # 1955 - - CTC CAC CAG TGG ATT AAT GAA GAC TGC TCC AC - #A CCG TGT TCC GGC TCG 6257 Leu His Gln Trp Ile Asn Glu Asp Cys Ser Th - #r Pro Cys Ser Gly Ser 1960 1965 - # 1970 - # 1975 - - TGG CTA AGG GAT GTT TGG GAC TGG ATA TGC AC - #G GTG TTG ACT GAC TTC 6305 Trp Leu Arg Asp Val Trp Asp Trp Ile Cys Th - #r Val Leu Thr Asp Phe 1980 - # 1985 - # 1990 - - AAG ACC TGG CTC CAG TCC AAG CTC CTG CCG CA - #G CTA CCT GGA GTC CCT 6353 Lys Thr Trp Leu Gln Ser Lys Leu Leu Pro Gl - #n Leu Pro Gly Val Pro 1995 - # 2000 - # 2005 - - TTT TTC TCG TGC CAA CGC GGG TAC AAG GGA GT - #C TGG CGG GGA GAC GGC 6401 Phe Phe Ser Cys Gln Arg Gly Tyr Lys Gly Va - #l Trp Arg Gly Asp Gly 2010 - # 2015 - # 2020 - - ATC ATG CAA ACC ACC TGC CCA TGT GGA GCA CA - #G ATC ACC GGA CAT GTC 6449 Ile Met Gln Thr Thr Cys Pro Cys Gly Ala Gl - #n Ile Thr Gly His Val 2025 - # 2030 - # 2035 - - AAA AAC GGT TCC ATG AGG ATC GTC GGG CCT AA - #G ACC TGC AGC AAC ACG 6497 Lys Asn Gly Ser Met Arg Ile Val Gly Pro Ly - #s Thr Cys Ser Asn Thr 2040 2045 - # 2050 - # 2055 - - TGG CAT GGA ACA TTC CCC ATC AAC GCA TAC AC - #C ACG GGC CCC TGC ACA 6545 Trp His Gly Thr Phe Pro Ile Asn Ala Tyr Th - #r Thr Gly Pro Cys Thr 2060 - # 2065 - # 2070 - - CCC TCT CCA GCG CCA AAC TAT TCT AGG GCG CT - #G TGG CGG GTG GCC GCT 6593 Pro Ser Pro Ala Pro Asn Tyr Ser Arg Ala Le - #u Trp Arg Val Ala Ala 2075 - # 2080 - # 2085 - - GAG GAG TAC GTG GAG GTC ACG CGG GTG GGG GA - #T TTC CAC TAC GTG ACG 6641 Glu Glu Tyr Val Glu Val Thr Arg Val Gly As - #p Phe His Tyr Val Thr 2090 - # 2095 - # 2100 - - GGC ATG ACC ACT GAC AAC GTA AAG TGC CCA TG - #C CAG GTT CCG GCT CCT 6689 Gly Met Thr Thr Asp Asn Val Lys Cys Pro Cy - #s Gln Val Pro Ala Pro 2105 - # 2110 - # 2115 - - GAA TTC TTC TCG GAG GTG GAC GGA GTG CGG TT - #G CAC AGG TAC GCT CCG 6737 Glu Phe Phe Ser Glu Val Asp Gly Val Arg Le - #u His Arg Tyr Ala Pro 2120 2125 - # 2130 - # 2135 - - GCG TGC AGG CCT CTC CTA CGG GAG GAG GTT AC - #A TTC CAG GTC GGG CTC 6785 Ala Cys Arg Pro Leu Leu Arg Glu Glu Val Th - #r Phe Gln Val Gly Leu 2140 - # 2145 - # 2150 - - AAC CAA TAC CTG GTT GGG TCA CAG CTA CCA TG - #C GAG CCC GAA CCG GAT 6833 Asn Gln Tyr Leu Val Gly Ser Gln Leu Pro Cy - #s Glu Pro Glu Pro Asp 2155 - # 2160 - # 2165 - - GTA GCA GTG CTC ACT TCC ATG CTC ACC GAC CC - #C TCC CAC ATC ACA GCA 6881 Val Ala Val Leu Thr Ser Met Leu Thr Asp Pr - #o Ser His Ile Thr Ala 2170 - # 2175 - # 2180 - - GAA ACG GCT AAG CGT AGG TTG GCC AGG GGG TC - #T CCC CCC TCC TTG GCC 6929 Glu Thr Ala Lys Arg Arg Leu Ala Arg Gly Se - #r Pro Pro Ser Leu Ala 2185 - # 2190 - # 2195 - - AGC TCT TCA GCT AGC CAG TTG TCT GCG CCT TC - #C TTG AAG GCG ACA TGC 6977 Ser Ser Ser Ala Ser Gln Leu Ser Ala Pro Se - #r Leu Lys Ala Thr Cys 2200 2205 - # 2210 - # 2215 - - ACT ACC CAC CAT GTC TCT CCG GAC GCT GAC CT - #C ATC GAG GCC AAC CTC 7025 Thr Thr His His Val Ser Pro Asp Ala Asp Le - #u Ile Glu Ala Asn Leu 2220 - # 2225 - # 2230 - - CTG TGG CGG CAG GAG ATG GGC GGG AAC ATC AC - #C CGC GTG GAG TCG GAG 7073 Leu Trp Arg Gln Glu Met Gly Gly Asn Ile Th - #r Arg Val Glu Ser Glu 2235 - # 2240 - # 2245 - - AAC AAG GTG GTA GTC CTG GAC TCT TTC GAC CC - #G CTT CGA GCG GAG GAG 7121 Asn Lys Val Val Val Leu Asp Ser Phe Asp Pr - #o Leu Arg Ala Glu Glu 2250 - # 2255 - # 2260 - - GAT GAG AGG GAA GTA TCC GTT CCG GCG GAG AT - #C CTG CGG AAA TCC AAG 7169 Asp Glu Arg Glu Val Ser Val Pro Ala Glu Il - #e Leu Arg Lys Ser Lys 2265 - # 2270 - # 2275 - - AAG TTC CCC GCA GCG ATG CCC ATC TGG GCG CG - #C CCG GAT TAC AAC CCT 7217 Lys Phe Pro Ala Ala Met Pro Ile Trp Ala Ar - #g Pro Asp Tyr Asn Pro 2280 2285 - # 2290 - # 2295 - - CCA CTG TTA GAG TCC TGG AAG GAC CCG GAC TA - #C GTC CCT CCG GTG GTG 7265 Pro Leu Leu Glu Ser Trp Lys Asp Pro Asp Ty - #r Val Pro Pro Val Val 2300 - # 2305 - # 2310 - - CAC GGG TGC CCG TTG CCA CCT ATC AAG GCC CC - #T CCA ATA CCA CCT CCA 7313 His Gly Cys Pro Leu Pro Pro Ile Lys Ala Pr - #o Pro Ile Pro Pro Pro 2315 - # 2320 - # 2325 - - CGG AGA AAG AGG ACG GTT GTC CTA ACA GAG TC - #C TCC GTG TCT TCT GCC 7361 Arg Arg Lys Arg Thr Val Val Leu Thr Glu Se - #r Ser Val Ser Ser Ala 2330 - # 2335 - # 2340 - - TTA GCG GAG CTC GCT ACT AAG ACC TTC GGC AG - #C TCC GAA TCA TCG GCC 7409 Leu Ala Glu Leu Ala Thr Lys Thr Phe Gly Se - #r Ser Glu Ser Ser Ala 2345 - # 2350 - # 2355 - - GTC GAC AGC GGC ACG GCG ACC GCC CTT CCT GA - #C CAG GCC TCC GAC GAC 7457 Val Asp Ser Gly Thr Ala Thr Ala Leu Pro As - #p Gln Ala Ser Asp Asp 2360 2365 - # 2370 - # 2375 - - GGT GAC AAA GGA TCC GAC GTT GAG TCG TAC TC - #C TCC ATG CCC CCC CTT 7505 Gly Asp Lys Gly Ser Asp Val Glu Ser Tyr Se - #r Ser Met Pro Pro Leu 2380 - # 2385 - # 2390 - - GAG GGG GAA CCG GGG GAC CCC GAT CTC AGT GA - #C GGG TCT TGG TCT ACC 7553 Glu Gly Glu Pro Gly Asp Pro Asp Leu Ser As - #p Gly Ser Trp Ser Thr 2395 - # 2400 - # 2405 - - GTG AGC GAG GAA GCT AGT GAG GAT GTC GTC TG - #C TGC TCA ATG TCC TAC 7601 Val Ser Glu Glu Ala Ser Glu Asp Val Val Cy - #s Cys Ser Met Ser Tyr 2410 - # 2415 - # 2420 - - ACA TGG ACA GGC GCC TTG ATC ACG CCA TGC GC - #T GCG GAG GAA AGC AAG 7649 Thr Trp Thr Gly Ala Leu Ile Thr Pro Cys Al - #a Ala Glu Glu Ser Lys 2425 - # 2430 - # 2435 - - CTG CCC ATC AAC GCG TTG AGC AAC TCT TTG CT - #G CGC CAC CAT AAC ATG 7697 Leu Pro Ile Asn Ala Leu Ser Asn Ser Leu Le - #u Arg His His Asn Met 2440 2445 - # 2450 - # 2455 - - GTT TAT GCC ACA ACA TCT CGC AGC GCA GGC CT - #G CGG CAG AAG AAG GTC 7745 Val Tyr Ala Thr Thr Ser Arg Ser Ala Gly Le - #u Arg Gln Lys Lys Val 2460 - # 2465 - # 2470 - - ACC TTT GAC AGA CTG CAA GTC CTG GAC GAC CA - #C TAC CGG GAC GTG CTC 7793 Thr Phe Asp Arg Leu Gln Val Leu Asp Asp Hi - #s Tyr Arg Asp Val Leu 2475 - # 2480 - # 2485 - - AAG GAG ATG AAG GCG AAG GCG TCC ACA GTT AA - #G GCT AAA CTC CTA TCC 7841 Lys Glu Met Lys Ala Lys Ala Ser Thr Val Ly - #s Ala Lys Leu Leu Ser 2490 - # 2495 - # 2500 - - GTA GAG GAA GCC TGC AAG CTG ACG CCC CCA CA - #T TCG GCC AAA TCC AAG 7889 Val Glu Glu Ala Cys Lys Leu Thr Pro Pro Hi - #s Ser Ala Lys Ser Lys 2505 - # 2510 - # 2515 - - TTT GGC TAT GGG GCA AAG GAC GTC CGG AAC CT - #A TCC AGC AAG GCC GTT 7937 Phe Gly Tyr Gly Ala Lys Asp Val Arg Asn Le - #u Ser Ser Lys Ala Val 2520 2525 - # 2530 - # 2535 - - AAC CAC ATC CAC TCC GTG TGG AAG GAC TTG CT - #G GAA GAC ACT GTG ACA 7985 Asn His Ile His Ser Val Trp Lys Asp Leu Le - #u Glu Asp Thr Val Thr 2540 - # 2545 - # 2550 - - CCA ATT GAC ACC ACC ATC ATG GCA AAA AAT GA - #G GTT TTC TGT GTC CAA 8033 Pro Ile Asp Thr Thr Ile Met Ala Lys Asn Gl - #u Val Phe Cys Val Gln 2555 - # 2560 - # 2565 - - CCA GAG AAA GGA GGC CGT AAG CCA GCC CGC CT - #T ATC GTA TTC CCA GAT 8081 Pro Glu Lys Gly Gly Arg Lys Pro Ala Arg Le - #u Ile Val Phe Pro Asp 2570 - # 2575 - # 2580 - - CTG GGA GTC CGT GTA TGC GAG AAG ATG GCC CT - #C TAT GAT GTG GTC TCC 8129 Leu Gly Val Arg Val Cys Glu Lys Met Ala Le - #u Tyr Asp Val Val Ser 2585 - # 2590 - # 2595 - - ACC CTT CCT CAG GTC GTG ATG GGC TCC TCA TA - #C GGA TTC CAG TAC TCT 8177 Thr Leu Pro Gln Val Val Met Gly Ser Ser Ty - #r Gly Phe Gln Tyr Ser 2600 2605 - # 2610 - # 2615 - - CCT GGG CAG CGA GTC GAG TTC CTG GTG AAT AC - #C TGG AAA TCA AAG AAA 8225 Pro Gly Gln Arg Val Glu Phe Leu Val Asn Th - #r Trp Lys Ser Lys Lys 2620 - # 2625 - # 2630 - - AAC CCC ATG GGC TTT TCA TAT GAC ACT CGC TG - #T TTC GAC TCA ACG GTC 8273 Asn Pro Met Gly Phe Ser Tyr Asp Thr Arg Cy - #s Phe Asp Ser Thr Val 2635 - # 2640 - # 2645 - - ACC GAG AAC GAC ATC CGT GTT GAG GAG TCA AT - #T TAC CAA TGT TGT GAC 8321 Thr Glu Asn Asp Ile Arg Val Glu Glu Ser Il - #e Tyr Gln Cys Cys Asp 2650 - # 2655 - # 2660 - - TTG GCC CCC GAA GCC AGA CAG GCC ATA AAA TC - #G CTC ACA GAG CGG CTT 8369 Leu Ala Pro Glu Ala Arg Gln Ala Ile Lys Se - #r Leu Thr Glu Arg Leu 2665 - # 2670 - # 2675 - - TAT ATC GGG GGT CCT CTG ACT AAT TCA AAA GG - #G CAG AAC TGC GGT TAT 8417 Tyr Ile Gly Gly Pro Leu Thr Asn Ser Lys Gl - #y Gln Asn Cys Gly Tyr 2680 2685 - # 2690 - # 2695 - - CGC CGG TGC CGC GCG AGC GGC GTG CTG ACG AC - #T AGC TGC GGT AAC ACC 8465 Arg Arg Cys Arg Ala Ser Gly Val Leu Thr Th - #r Ser Cys Gly Asn Thr 2700 - # 2705 - # 2710 - - CTC ACA TGT TAC TTG AAG GCC TCT GCA GCC TG - #T CGA GCT GCG AAG CTC 8513 Leu Thr Cys Tyr Leu Lys Ala Ser Ala Ala Cy - #s Arg Ala Ala Lys Leu 2715 - # 2720 - # 2725 - - CAG GAC TGC ACG ATG CTC GTG AAC GGA GAC GA - #C CTC GTC GTT ATC TGT 8561 Gln Asp Cys Thr Met Leu Val Asn Gly Asp As - #p Leu Val Val Ile Cys 2730 - # 2735 - # 2740 - - GAA AGC GCG GGA ACC CAA GAG GAC GCG GCG AG - #C CTA CGA GTC TTC ACG 8609 Glu Ser Ala Gly Thr Gln Glu Asp Ala Ala Se - #r Leu Arg Val Phe Thr 2745 - # 2750 - # 2755 - - GAG GCT ATG ACT AGG TAC TCC GCC CCC CCC GG - #G GAC CCG CCC CAA CCA 8657 Glu Ala Met Thr Arg Tyr Ser Ala Pro Pro Gl - #y Asp Pro Pro Gln Pro 2760 2765 - # 2770 - # 2775 - - GAA TAC GAC TTG GAG CTG ATA ACA TCA TGT TC - #C TCC AAT GTG TCG GTC 8705 Glu Tyr Asp Leu Glu Leu Ile Thr Ser Cys Se - #r Ser Asn Val Ser Val 2780 - # 2785 - # 2790 - - GCC CAC GAT GCA TCA GGC AAA AGG GTG TAC TA - #C CTC ACC CGT GAT CCC 8753 Ala His Asp Ala Ser Gly Lys Arg Val Tyr Ty - #r Leu Thr Arg Asp Pro 2795 - # 2800 - # 2805 - - ACC ACC CCC CTA GCA CGG GCT GCG TGG GAG AC - #A GCT AGA CAC ACT CCA 8801 Thr Thr Pro Leu Ala Arg Ala Ala Trp Glu Th - #r Ala Arg His Thr Pro 2810 - # 2815 - # 2820 - - GTT AAC TCC TGG CTA GGC AAC ATT ATT ATG TA - #T GCG CCC ACT TTG TGG 8849 Val Asn Ser Trp Leu Gly Asn Ile Ile Met Ty - #r Ala Pro Thr Leu Trp 2825 - # 2830 - # 2835 - - GCA AGG ATG ATT CTG ATG ACT CAC TTC TTC TC - #C ATC CTT CTA GCG CAG 8897 Ala Arg Met Ile Leu Met Thr His Phe Phe Se - #r Ile Leu Leu Ala Gln 2840 2845 - # 2850 - # 2855 - - GAG CAA CTT GAA AAA GCC CTG GAC TGC CAG AT - #C TAC GGG GCC TGT TAC 8945 Glu Gln Leu Glu Lys Ala Leu Asp Cys Gln Il - #e Tyr Gly Ala Cys Tyr 2860 - # 2865 - # 2870 - - TCC ATT GAG CCA CTT GAC CTA CCT CAG ATC AT - #T GAA CGA CTC CAT GGC 8993 Ser Ile Glu Pro Leu Asp Leu Pro Gln Ile Il - #e Glu Arg Leu His Gly 2875 - # 2880 - # 2885 - - CTT AGC GCA TTT TCA CTC CAT AGT TAC TCT CC - #A GGT GAG ATC AAT AGG 9041 Leu Ser Ala Phe Ser Leu His Ser Tyr Ser Pr - #o Gly Glu Ile Asn Arg 2890 - # 2895 - # 2900 - - GTG GCT TCA TGC CTC AGG AAA CTT GGG GTA CC - #A CCC TTG CGA GTC TGG 9089 Val Ala Ser Cys Leu Arg Lys Leu Gly Val Pr - #o Pro Leu Arg Val Trp 2905 - # 2910 - # 2915 - - AGA CAT CGG GCC AGG AGC GTC CGC GCT AGG CT - #A CTG TCC CAG GGA GGG 9137 Arg His Arg Ala Arg Ser Val Arg Ala Arg Le - #u Leu Ser Gln Gly Gly 2920 2925 - # 2930 - # 2935 - - AGG GCC GCC ACT TGT GGC AAA TAC CTC TTC AA - #C TGG GCA GTA AAA ACC 9185 Arg Ala Ala Thr Cys Gly Lys Tyr Leu Phe As - #n Trp Ala Val Lys Thr 2940 - # 2945 - # 2950 - - AAA CTT AAA CTC ACT CCA ATC CCG GCT GCG TC - #C CGG CTG GAC TTG TCC 9233 Lys Leu Lys Leu Thr Pro Ile Pro Ala Ala Se - #r Arg Leu Asp Leu Ser 2955 - # 2960 - # 2965 - - GGC TGG TTC GTT GCT GGT TAC AGC GGG GGA GA - #C ATA TAT CAC AGC CTG 9281 Gly Trp Phe Val Ala Gly Tyr Ser Gly Gly As - #p Ile Tyr His Ser Leu 2970 - # 2975 - # 2980 - - TCT CGT GCC CGA CCC CGT TGG TTC ATG CTG TG - #C CTA CTC CTA CTT TCT 9329 Ser Arg Ala Arg Pro Arg Trp Phe Met Leu Cy - #s Leu Leu Leu Leu Ser 2985 - # 2990 - # 2995 - - GTA GGG GTA GGC ATC TAC CTG CTC CCC AAC CG - #A TGAACGGGGA GATAAACACT 9382 Val Gly Val Gly Ile Tyr Leu Leu Pro Asn Ar - #g 3000 3005 - # 3010 - - CCAGGCCAAT AGGCCATCCC CCTTTTTTTT TTTT - # -# 9416 - - - - (2) INFORMATION FOR SEQ ID NO:2: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3010 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: - - Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Th - #r Lys Arg Asn ThrAsn 1 5 - # 10 - # 15 - - Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gl - #y Gly Gln Ile Val Gly 20 - # 25 - # 30 - - Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Ar - #g Leu Gly Val Arg Ala 35 - # 40 - # 45 - - Pro Arg Lys Thr Ser Glu Arg Ser Gln Pro Ar - #g Gly Arg Arg Gln Pro 50 - # 55 - # 60 - - Ile Pro Lys Ala Arg Arg Pro Glu Gly Arg Th - #r Trp Ala Gln Pro Gly 65 - # 70 - # 75 - # 80 - - Tyr Pro Trp Pro Leu Tyr Gly Asn Glu Gly Le - #u Gly Trp Ala Gly Trp 85 - # 90 - # 95 - - Leu Leu Ser Pro Arg Gly Ser Arg Pro Ser Tr - #p Gly Pro Thr Asp Pro 100 - # 105 - # 110 - - Arg Arg Arg Ser Arg Asn Leu Gly Lys Val Il - #e Asp Thr Leu Thr Cys 115 - # 120 - # 125 - - Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Le - #u Val Gly Ala Pro Leu 130 - # 135 - # 140 - - Gly Gly Ala Ala Arg Ala Leu Ala His Gly Va - #l Arg Val Leu Glu Asp 145 1 - #50 1 - #55 1 -#60 - - Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gl - #y Cys Ser Phe SerIle 165 - # 170 - # 175 - - Phe Leu Leu Ala Leu Leu Ser Cys Leu Thr Th - #r Pro Ala Ser Ala Tyr 180 - # 185 - # 190 - - Glu Val His Asn Val Ser Gly Ile Tyr His Va - #l Thr Asn Asp Cys Ser 195 - # 200 - # 205 - - Asn Ala Ser Ile Val Tyr Glu Ala Ala Asp Le - #u Ile Met His Thr Pro 210 - # 215 - # 220 - - Gly Cys Val Pro Cys Val Arg Glu Gly Asn Se - #r Ser Arg Cys Trp Val 225 2 - #30 2 - #35 2 -#40 - - Ala Leu Thr Pro Thr Leu Ala Ala Arg Asn Va - #l Thr Ile Pro ThrThr 245 - # 250 - # 255 - - Thr Ile Arg Arg His Val Asp Leu Leu Val Gl - #y Ala Ala Ala Phe Cys 260 - # 265 - # 270 - - Ser Ala Met Tyr Val Gly Asp Leu Cys Gly Se - #r Val Phe Leu Val Ser 275 - # 280 - # 285 - - Gln Leu Phe Thr Phe Ser Pro Arg Arg His Va - #l Thr Leu Gln Asp Cys 290 - # 295 - # 300 - - Asn Cys Ser Ile Tyr Pro Gly His Val Ser Gl - #y His Arg Met Ala Trp 305 3 - #10 3 - #15 3 -#20 - - Asp Met Met Met Asn Trp Ser Pro Thr Thr Al - #a Leu Val Val SerGln 325 - # 330 - # 335 - - Leu Leu Arg Ile Pro Gln Ala Val Val Asp Me - #t Val Ala Gly Ala His 340 - # 345 - # 350 - - Trp Gly Val Leu Ala Gly Leu Ala Tyr Tyr Se - #r Met Ala Gly Asn Trp 355 - # 360 - # 365 - - Ala Lys Val Leu Ile Val Met Leu Leu Phe Al - #a Gly Val Asp Gly Asp 370 - # 375 - # 380 - - Thr His Val Thr Gly Gly Ala Gln Ala Lys Th - #r Thr Asn Arg Leu Val 385 3 - #90 3 - #95 4 -#00 - - Ser Met Phe Ala Ser Gly Pro Ser Gln Lys Il - #e Gln Leu Ile AsnThr 405 - # 410 - # 415 - - Asn Gly Ser Trp His Ile Asn Arg Thr Ala Le - #u Asn Cys Asn Asp Ser 420 - # 425 - # 430 - - Leu Gln Thr Gly Phe Leu Ala Ala Leu Phe Ty - #r Thr His Ser Phe Asn 435 - # 440 - # 445 - - Ser Ser Gly Cys Pro Glu Arg Met Ala Gln Cy - #s Arg Thr Ile Asp Lys 450 - # 455 - # 460 - - Phe Asp Gln Gly Trp Gly Pro Ile Thr Tyr Al - #a Glu Ser Ser Arg Ser 465 4 - #70 4 - #75 4 -#80 - - Asp Gln Arg Pro Tyr Cys Trp His Tyr Pro Pr - #o Pro Gln Cys ThrIle 485 - # 490 - # 495 - - Val Pro Ala Ser Glu Val Cys Gly Pro Val Ty - #r Cys Phe Thr Pro Ser 500 - # 505 - # 510 - - Pro Val Val Val Gly Thr Thr Asp Arg Phe Gl - #y Val Pro Thr Tyr Arg 515 - # 520 - # 525 - - Trp Gly Glu Asn Glu Thr Asp Val Leu Leu Le - #u Asn Asn Thr Arg Pro 530 - # 535 - # 540 - - Pro Gln Gly Asn Trp Phe Gly Cys Thr Trp Me - #t Asn Ser Thr Gly Phe 545 5 - #50 5 - #55 5 -#60 - - Thr Lys Thr Cys Gly Gly Pro Pro Cys Asn Il - #e Gly Gly Val GlyAsn 565 - # 570 - # 575 - - Asn Thr Leu Thr Cys Pro Thr Asp Cys Phe Ar - #g Lys His Pro Glu Ala 580 - # 585 - # 590 - - Thr Tyr Thr Lys Cys Gly Ser Gly Pro Trp Le - #u Thr Pro Arg Cys Met 595 - # 600 - # 605 - - Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pr - #o Cys Thr Val Asn Phe 610 - # 615 - # 620 - - Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gl - #y Val Glu His Arg Leu 625 6 - #30 6 - #35 6 -#40 - - Asn Ala Ala Cys Asn Trp Thr Arg Gly Glu Ar - #g Cys Asp Leu GluAsp 645 - # 650 - # 655 - - Arg Asp Arg Pro Glu Leu Ser Pro Leu Leu Le - #u Ser Thr Thr Glu Trp 660 - # 665 - # 670 - - Gln Val Leu Pro Cys Ser Phe Thr Thr Leu Pr - #o Ala Leu Ser Thr Gly 675 - # 680 - # 685 - - Leu Ile His Leu His Gln Asn Ile Val Asp Va - #l Gln Tyr Leu Tyr Gly 690 - # 695 - # 700 - - Ile Gly Ser Ala Val Val Ser Phe Ala Ile Ly - #s Trp Glu Tyr Val Leu 705 7 - #10 7 - #15 7 -#20 - - Leu Leu Phe Leu Leu Leu Ala Asp Ala Arg Va - #l Cys Ala Cys LeuTrp 725 - # 730 - # 735 - - Met Met Leu Leu Ile Ala Gln Ala Glu Ala Al - #a Leu Glu Asn Leu Val 740 - # 745 - # 750 - - Val Leu Asn Ser Ala Ser Val Ala Gly Ala Hi - #s Gly Ile Leu Ser Phe 755 - # 760 - # 765 - - Leu Val Phe Phe Cys Ala Ala Trp Tyr Ile Ly - #s Gly Arg Leu Val Pro 770 - # 775 - # 780 - - Gly Ala Thr Tyr Ala Leu Tyr Gly Val Trp Pr - #o Leu Leu Leu Leu Leu 785 7 - #90 7 - #95 8 -#00 - - Leu Ala Leu Pro Pro Arg Ala Tyr Ala Met As - #p Arg Glu Met AlaAla 805 - # 810 - # 815 - - Ser Cys Gly Gly Ala Val Phe Val Gly Leu Va - #l Leu Leu Thr Leu Ser 820 - # 825 - # 830 - - Pro Tyr Tyr Lys Val Phe Leu Ala Arg Leu Il - #e Trp Trp Leu Gln Tyr 835 - # 840 - # 845 - - Phe Thr Thr Arg Ala Glu Ala Asp Leu His Va - #l Trp Ile Pro Pro Leu 850 - # 855 - # 860 - - Asn Ala Arg Gly Gly Arg Asp Ala Ile Ile Le - #u Leu Met Cys Ala Val 865 8 - #70 8 - #75 8 -#80 - - His Pro Glu Leu Ile Phe Asp Ile Thr Lys Le - #u Leu Ile Ala IleLeu 885 - # 890 - # 895 - - Gly Pro Leu Met Val Leu Gln Ala Gly Ile Th - #r Arg Val Pro Tyr Phe 900 - # 905 - # 910 - - Val Arg Ala Gln Gly Leu Ile His Ala Cys Me - #t Leu Val Arg Lys Val 915 - # 920 - # 925 - - Ala Gly Gly His Tyr Val Gln Met Ala Phe Me - #t Lys Leu Gly Ala Leu 930 - # 935 - # 940 - - Thr Gly Thr Tyr Ile Tyr Asn His Leu Thr Pr - #o Leu Arg Asp Trp Pro 945 9 - #50 9 - #55 9 -#60 - - Arg Ala Gly Leu Arg Asp Leu Ala Val Ala Va - #l Glu Pro Val ValPhe 965 - # 970 - # 975 - - Ser Asp Met Glu Thr Lys Ile Ile Thr Trp Gl - #y Ala Asp Thr Ala Ala 980 - # 985 - # 990 - - Cys Gly Asp Ile Ile Leu Gly Leu Pro Val Se - #r Ala Arg Arg Gly Lys 995 - # 1000 - # 1005 - - Glu Ile Leu Leu Gly Pro Ala Asp Ser Leu Gl - #u Gly Arg Gly Leu Arg 1010 - # 1015 - # 1020 - - Leu Leu Ala Pro Ile Thr Ala Tyr Ser Gln Gl - #n Thr Arg Gly Leu Leu 1025 1030 - # 1035 - # 1040 - - Gly Cys Ile Ile Thr Ser Leu Thr Gly Arg As - #p Lys Asn Gln Val Glu 1045 - # 1050 - # 1055 - - Gly Glu Val Gln Val Val Ser Thr Ala Thr Gl - #n Ser Phe Leu Ala Thr 1060 - # 1065 - # 1070 - - Cys Val Asn Gly Val Cys Trp Thr Val Tyr Hi - #s Gly Ala Gly Ser Lys 1075 - # 1080 - # 1085 - - Thr Leu Ala Ala Pro Lys Gly Pro Ile Thr Gl - #n Met Tyr Thr Asn Val 1090 - # 1095 - # 1100 - - Asp Gln Asp Leu Val Gly Trp Pro Lys Pro Pr - #o Gly Ala Arg Ser Leu 1105 1110 - # 1115 - # 1120 - - Thr Pro Cys Thr Cys Gly Ser Ser Asp Leu Ty - #r Leu Val Thr Arg His 1125 - # 1130 - # 1135 - - Ala Asp Val Ile Pro Val Arg Arg Arg Gly As - #p Ser Arg Gly Ser Leu 1140 - # 1145 - # 1150 - - Leu Ser Pro Arg Pro Val Ser Tyr Leu Lys Gl - #y Ser Ser Gly Gly Pro 1155 - # 1160 - # 1165 - - Leu Leu Cys Pro Phe Gly His Ala Val Gly Il - #e Phe Arg Ala Ala Val 1170 - # 1175 - # 1180 - - Cys Thr Arg Gly Val Ala Lys Ala Val Asp Ph - #e Val Pro Val Glu Ser 1185 1190 - # 1195 - # 1200 - - Met Glu Thr Thr Met Arg Ser Pro Val Phe Th - #r Asp Asn Ser Ser Pro 1205 - # 1210 - # 1215 - - Pro Ala Val Pro Gln Ser Phe Gln Val Ala Hi - #s Leu His Ala Pro Thr 1220 - # 1225 - # 1230 - - Gly Ser Gly Lys Ser Thr Lys Val Pro Ala Al - #a Tyr Ala Ala Gln Gly 1235 - # 1240 - # 1245 - - Tyr Lys Val Leu Val Leu Asn Pro Ser Val Al - #a Ala Thr Leu Gly Phe 1250 - # 1255 - # 1260 - - Gly Ala Tyr Met Ser Lys Ala His Gly Ile As - #p Pro Asn Ile Arg Thr 1265 1270 - # 1275 - # 1280 - - Gly Val Arg Thr Ile Thr Thr Gly Ala Pro Va - #l Thr Tyr Ser Thr Tyr 1285 - # 1290 - # 1295 - - Gly Lys Phe Leu Ala Asp Gly Gly Cys Ser Gl - #y Gly Ala Tyr Asp Ile 1300 - # 1305 - # 1310 - - Ile Ile Cys Asp Glu Cys His Ser Thr Asp Se - #r Thr Thr Ile Leu Gly 1315 - # 1320 - # 1325 - - Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Al - #a Gly Ala Arg Leu Val 1330 - # 1335 - # 1340 - - Val Leu Ala Thr Ala Thr Pro Pro Gly Ser Va - #l Thr Val Pro His Pro 1345 1350 - # 1355 - # 1360 - - Asn Ile Glu Glu Val Ala Leu Ser Asn Thr Gl - #y Glu Ile Pro Phe Tyr 1365 - # 1370 - # 1375 - - Gly Lys Ala Ile Pro Ile Glu Ala Ile Arg Gl - #y Gly Arg His Leu Ile 1380 - # 1385 - # 1390 - - Phe Cys His Ser Lys Lys Lys Cys Asp Glu Le - #u Ala Ala Lys Leu Ser 1395 - # 1400 - # 1405 - - Gly Leu Gly Ile Asn Ala Val Ala Tyr Tyr Ar - #g Gly Leu Asp Val Ser 1410 - # 1415 - # 1420 - - Val Ile Pro Thr Ile Gly Asp Val Val Val Va - #l Ala Thr Asp Ala Leu 1425 1430 - # 1435 - # 1440 - - Met Thr Gly Tyr Thr Gly Asp Phe Asp Ser Va - #l Ile Asp Cys Asn Thr 1445 - # 1450 - # 1455 - - Cys Val Thr Gln Thr Val Asp Phe Ser Leu As - #p Pro Thr Phe Thr Ile 1460 - # 1465 - # 1470 - - Glu Thr Thr Thr Val Pro Gln Asp Ala Val Se - #r Arg Ser Gln Arg Arg 1475 - # 1480 - # 1485 - - Gly Arg Thr Gly Arg Gly Arg Arg Gly Ile Ty - #r Arg Phe Val Thr Pro 1490 - # 1495 - # 1500 - - Gly Glu Arg Pro Ser Gly Met Phe Asp Ser Se - #r Val Leu Cys Glu Cys 1505 1510 - # 1515 - # 1520 - - Tyr Asp Ala Gly Cys Ala Trp Tyr Glu Leu Th - #r Pro Ala Glu Thr Ser 1525 - # 1530 - # 1535 - - Val Arg Leu Arg Ala Tyr Leu Asn Thr Pro Gl - #y Leu Pro Val Cys Gln 1540 - # 1545 - # 1550 - - Asp His Leu Glu Phe Trp Glu Ser Val Phe Th - #r Gly Leu Thr His Ile 1555 - # 1560 - # 1565 - - Asp Ala His Phe Leu Ser Gln Thr Lys Gln Al - #a Gly Asp Asn Phe Pro 1570 - # 1575 - # 1580 - - Tyr Leu Val Ala Tyr Gln Ala Thr Val Cys Al - #a Arg Ala Gln Ala Pro 1585 1590 - # 1595 - # 1600 - - Pro Pro Ser Trp Asp Gln Met Trp Lys Cys Le - #u Ile Arg Leu Lys Pro 1605 - # 1610 - # 1615 - - Thr Leu His Gly Pro Thr Pro Leu Leu Tyr Ar - #g Leu Gly Ala Val Gln 1620 - # 1625 - # 1630 - - Asn Glu Val Thr Leu Thr His Pro Ile Thr Ly - #s Tyr Ile Met Ala Cys 1635 - # 1640 - # 1645 - - Met Ser Ala Asp Leu Glu Val Val Thr Ser Th - #r Trp Val Leu Val Gly 1650 - # 1655 - # 1660 - - Gly Val Leu Ala Ala Leu Ala Ala Tyr Cys Le - #u Thr Thr Gly Ser Val 1665 1670 - # 1675 - # 1680 - - Val Ile Val Gly Arg Ile Ile Leu Ser Gly Ar - #g Pro Ala Ile Val Pro 1685 - # 1690 - # 1695 - - Asp Arg Glu Leu Leu Tyr Gln Glu Phe Asp Gl - #u Met Glu Glu Cys Ala 1700 - # 1705 - # 1710 - - Ser His Leu Pro Tyr Ile Glu Gln Gly Met Gl - #n Leu Ala Glu Gln Phe 1715 - # 1720 - # 1725 - - Lys Gln Lys Ala Leu Gly Leu Leu Gln Thr Al - #a Thr Lys Gln Ala Glu 1730 - # 1735 - # 1740 - - Ala Ala Ala Pro Val Val Glu Ser Lys Trp Ar - #g Ala Leu Glu Thr Phe 1745 1750 - # 1755 - # 1760 - - Trp Ala Lys His Met Trp Asn Phe Ile Ser Gl - #y Ile Gln Tyr Leu Ala 1765 - # 1770 - # 1775 - - Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Il - #e Ala Ser Leu Met Ala 1780 - # 1785 - # 1790 - - Phe Thr Ala Ser Ile Thr Ser Pro Leu Thr Th - #r Gln Ser Thr Leu Leu 1795 - # 1800 - # 1805 - - Phe Asn Ile Leu Gly Gly Trp Val Ala Ala Gl - #n Leu Ala Pro Pro Ser 1810 - # 1815 - # 1820 - - Ala Ala Ser Ala Phe Val Gly Ala Gly Ile Al - #a Gly Ala Ala Val Gly 1825 1830 - # 1835 - # 1840 - - Ser Ile Gly Leu Gly Lys Val Leu Val Asp Il - #e Leu Ala Gly Tyr Gly 1845 - # 1850 - # 1855 - - Ala Gly Val Ala Gly Ala Leu Val Ala Phe Ly - #s Val Met Ser Gly Glu 1860 - # 1865 - # 1870 - - Met Pro Ser Thr Glu Asp Leu Val Asn Leu Le - #u Pro Ala Ile Leu Ser 1875 - # 1880 - # 1885 - - Pro Gly Ala Leu Val Val Gly Val Val Cys Al - #a Ala Ile Leu Arg Arg 1890 - # 1895 - # 1900 - - His Val Gly Pro Gly Glu Gly Ala Val Gln Tr - #p Met Asn Arg Leu Ile 1905 1910 - # 1915 - # 1920 - - Ala Phe Ala Ser Arg Gly Asn His Val Ser Pr - #o Thr His Tyr Val Pro 1925 - # 1930 - # 1935 - - Glu Ser Asp Ala Ala Ala Arg Val Thr Gln Il - #e Leu Ser Ser Leu Thr 1940 - # 1945 - # 1950 - - Ile Thr Gln Leu Leu Lys Arg Leu His Gln Tr - #p Ile Asn Glu Asp Cys 1955 - # 1960 - # 1965 - - Ser Thr Pro Cys Ser Gly Ser Trp Leu Arg As - #p Val Trp Asp Trp Ile 1970 - # 1975 - # 1980 - - Cys Thr Val Leu Thr Asp Phe Lys Thr Trp Le - #u Gln Ser Lys Leu Leu 1985 1990 - # 1995 - # 2000 - - Pro Gln Leu Pro Gly Val Pro Phe Phe Ser Cy - #s Gln Arg Gly Tyr Lys 2005 - # 2010 - # 2015 - - Gly Val Trp Arg Gly Asp Gly Ile Met Gln Th - #r Thr Cys Pro Cys Gly 2020 - # 2025 - # 2030 - - Ala Gln Ile Thr Gly His Val Lys Asn Gly Se - #r Met Arg Ile Val Gly 2035 - # 2040 - # 2045 - - Pro Lys Thr Cys Ser Asn Thr Trp His Gly Th - #r Phe Pro Ile Asn Ala 2050 - # 2055 - # 2060 - - Tyr Thr Thr Gly Pro Cys Thr Pro Ser Pro Al - #a Pro Asn Tyr Ser Arg 2065 2070 - # 2075 - # 2080 - - Ala Leu Trp Arg Val Ala Ala Glu Glu Tyr Va - #l Glu Val Thr Arg Val 2085 - # 2090 - # 2095 - - Gly Asp Phe His Tyr Val Thr Gly Met Thr Th - #r Asp Asn Val Lys Cys 2100 - # 2105 - # 2110 - - Pro Cys Gln Val Pro Ala Pro Glu Phe Phe Se - #r Glu Val Asp Gly Val 2115 - # 2120 - # 2125 - - Arg Leu His Arg Tyr Ala Pro Ala Cys Arg Pr - #o Leu Leu Arg Glu Glu 2130 - # 2135 - # 2140 - - Val Thr Phe Gln Val Gly Leu Asn Gln Tyr Le - #u Val Gly Ser Gln Leu 2145 2150 - # 2155 - # 2160 - - Pro Cys Glu Pro Glu Pro Asp Val Ala Val Le - #u Thr Ser Met Leu Thr 2165 - # 2170 - # 2175 - - Asp Pro Ser His Ile Thr Ala Glu Thr Ala Ly - #s Arg Arg Leu Ala Arg 2180 - # 2185 - # 2190 - - Gly Ser Pro Pro Ser Leu Ala Ser Ser Ser Al - #a Ser Gln Leu Ser Ala 2195 - # 2200 - # 2205 - - Pro Ser Leu Lys Ala Thr Cys Thr Thr His Hi - #s Val Ser Pro Asp Ala 2210 - # 2215 - # 2220 - - Asp Leu Ile Glu Ala Asn Leu Leu Trp Arg Gl - #n Glu Met Gly Gly Asn 2225 2230 - # 2235 - # 2240 - - Ile Thr Arg Val Glu Ser Glu Asn Lys Val Va - #l Val Leu Asp Ser Phe 2245 - # 2250 - # 2255 - - Asp Pro Leu Arg Ala Glu Glu Asp Glu Arg Gl - #u Val Ser Val Pro Ala 2260 - # 2265 - # 2270 - - Glu Ile Leu Arg Lys Ser Lys Lys Phe Pro Al - #a Ala Met Pro Ile Trp 2275 - # 2280 - # 2285 - - Ala Arg Pro Asp Tyr Asn Pro Pro Leu Leu Gl - #u Ser Trp Lys Asp Pro 2290 - # 2295 - # 2300 - - Asp Tyr Val Pro Pro Val Val His Gly Cys Pr - #o Leu Pro Pro Ile Lys 2305 2310 - # 2315 - # 2320 - - Ala Pro Pro Ile Pro Pro Pro Arg Arg Lys Ar - #g Thr Val Val Leu Thr 2325 - # 2330 - # 2335 - - Glu Ser Ser Val Ser Ser Ala Leu Ala Glu Le - #u Ala Thr Lys Thr Phe 2340 - # 2345 - # 2350 - - Gly Ser Ser Glu Ser Ser Ala Val Asp Ser Gl - #y Thr Ala Thr Ala Leu 2355 - # 2360 - # 2365 - - Pro Asp Gln Ala Ser Asp Asp Gly Asp Lys Gl - #y Ser Asp Val Glu Ser 2370 - # 2375 - # 2380 - - Tyr Ser Ser Met Pro Pro Leu Glu Gly Glu Pr - #o Gly Asp Pro Asp Leu 2385 2390 - # 2395 - # 2400 - - Ser Asp Gly Ser Trp Ser Thr Val Ser Glu Gl - #u Ala Ser Glu Asp Val 2405 - # 2410 - # 2415 - - Val Cys Cys Ser Met Ser Tyr Thr Trp Thr Gl - #y Ala Leu Ile Thr Pro 2420 - # 2425 - # 2430 - - Cys Ala Ala Glu Glu Ser Lys Leu Pro Ile As - #n Ala Leu Ser Asn Ser 2435 - # 2440 - # 2445 - - Leu Leu Arg His His Asn Met Val Tyr Ala Th - #r Thr Ser Arg Ser Ala 2450 - # 2455 - # 2460 - - Gly Leu Arg Gln Lys Lys Val Thr Phe Asp Ar - #g Leu Gln Val Leu Asp 2465 2470 - # 2475 - # 2480 - - Asp His Tyr Arg Asp Val Leu Lys Glu Met Ly - #s Ala Lys Ala Ser Thr 2485 - # 2490 - # 2495 - - Val Lys Ala Lys Leu Leu Ser Val Glu Glu Al - #a Cys Lys Leu Thr Pro 2500 - # 2505 - # 2510 - - Pro His Ser Ala Lys Ser Lys Phe Gly Tyr Gl - #y Ala Lys Asp Val Arg 2515 - # 2520 - # 2525 - - Asn Leu Ser Ser Lys Ala Val Asn His Ile Hi - #s Ser Val Trp Lys Asp 2530 - # 2535 - # 2540 - - Leu Leu Glu Asp Thr Val Thr Pro Ile Asp Th - #r Thr Ile Met Ala Lys 2545 2550 - # 2555 - # 2560 - - Asn Glu Val Phe Cys Val Gln Pro Glu Lys Gl - #y Gly Arg Lys Pro Ala 2565 - # 2570 - # 2575 - - Arg Leu Ile Val Phe Pro Asp Leu Gly Val Ar - #g Val Cys Glu Lys Met 2580 - # 2585 - # 2590 - - Ala Leu Tyr Asp Val Val Ser Thr Leu Pro Gl - #n Val Val Met Gly Ser 2595 - # 2600 - # 2605 - - Ser Tyr Gly Phe Gln Tyr Ser Pro Gly Gln Ar - #g Val Glu Phe Leu Val 2610 - # 2615 - # 2620 - - Asn Thr Trp Lys Ser Lys Lys Asn Pro Met Gl - #y Phe Ser Tyr Asp Thr 2625 2630 - # 2635 - # 2640 - - Arg Cys Phe Asp Ser Thr Val Thr Glu Asn As - #p Ile Arg Val Glu Glu 2645 - # 2650 - # 2655 - - Ser Ile Tyr Gln Cys Cys Asp Leu Ala Pro Gl - #u Ala Arg Gln Ala Ile 2660 - # 2665 - # 2670 - - Lys Ser Leu Thr Glu Arg Leu Tyr Ile Gly Gl - #y Pro Leu Thr Asn Ser 2675 - # 2680 - # 2685 - - Lys Gly Gln Asn Cys Gly Tyr Arg Arg Cys Ar - #g Ala Ser Gly Val Leu 2690 - # 2695 - # 2700 - - Thr Thr Ser Cys Gly Asn Thr Leu Thr Cys Ty - #r Leu Lys Ala Ser Ala 2705 2710 - # 2715 - # 2720 - - Ala Cys Arg Ala Ala Lys Leu Gln Asp Cys Th - #r Met Leu Val Asn Gly 2725 - # 2730 - # 2735 - - Asp Asp Leu Val Val Ile Cys Glu Ser Ala Gl - #y Thr Gln Glu Asp Ala 2740 - # 2745 - # 2750 - - Ala Ser Leu Arg Val Phe Thr Glu Ala Met Th - #r Arg Tyr Ser Ala Pro 2755 - # 2760 - # 2765 - - Pro Gly Asp Pro Pro Gln Pro Glu Tyr Asp Le - #u Glu Leu Ile Thr Ser 2770 - # 2775 - # 2780 - - Cys Ser Ser Asn Val Ser Val Ala His Asp Al - #a Ser Gly Lys Arg Val 2785 2790 - # 2795 - # 2800 - - Tyr Tyr Leu Thr Arg Asp Pro Thr Thr Pro Le - #u Ala Arg Ala Ala Trp 2805 - # 2810 - # 2815 - - Glu Thr Ala Arg His Thr Pro Val Asn Ser Tr - #p Leu Gly Asn Ile Ile 2820 - # 2825 - # 2830 - - Met Tyr Ala Pro Thr Leu Trp Ala Arg Met Il - #e Leu Met Thr His Phe 2835 - # 2840 - # 2845 - - Phe Ser Ile Leu Leu Ala Gln Glu Gln Leu Gl - #u Lys Ala Leu Asp Cys 2850 - # 2855 - # 2860 - - Gln Ile Tyr Gly Ala Cys Tyr Ser Ile Glu Pr - #o Leu Asp Leu Pro Gln 2865 2870 - # 2875 - # 2880 - - Ile Ile Glu Arg Leu His Gly Leu Ser Ala Ph - #e Ser Leu His Ser Tyr 2885 - # 2890 - # 2895 - - Ser Pro Gly Glu Ile Asn Arg Val Ala Ser Cy - #s Leu Arg Lys Leu Gly 2900 - # 2905 - # 2910 - - Val Pro Pro Leu Arg Val Trp Arg His Arg Al - #a Arg Ser Val Arg Ala 2915 - # 2920 - # 2925 - - Arg Leu Leu Ser Gln Gly Gly Arg Ala Ala Th - #r Cys Gly Lys Tyr Leu 2930 - # 2935 - # 2940 - - Phe Asn Trp Ala Val Lys Thr Lys Leu Lys Le - #u Thr Pro Ile Pro Ala 2945 2950 - # 2955 - # 2960 - - Ala Ser Arg Leu Asp Leu Ser Gly Trp Phe Va - #l Ala Gly Tyr Ser Gly 2965 - # 2970 - # 2975 - - Gly Asp Ile Tyr His Ser Leu Ser Arg Ala Ar - #g Pro Arg Trp Phe Met 2980 - # 2985 - # 2990 - - Leu Cys Leu Leu Leu Leu Ser Val Gly Val Gl - #y Ile Tyr Leu Leu Pro 2995 - # 3000 - # 3005 - - Asn Arg 3010 - - - - (2) INFORMATION FOR SEQ ID NO:3: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1499 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 333..1499 - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..1499 (D) OTHER INFORMATION: - #/note= "sequence = 1 - 1499 of SEQ ID NO: - #1" - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3: - - CGATTGGGGG CGACACTCCA CCATAGATCA CTCCCCTGTG AGGAACTACT GT -#CTTCACGC 60 - - AGAAAGCGTC TAGCCATGGC GTTAGTATGA GTGTCGTGCA GCCTCCAGGA CC -#CCCCCTCC 120 - - CGGGAGAGCC ATAGTGGTCT GCGGAACCGG TGAGTACACC GGAATTGCCA GG -#ACGACCGG 180 - - GTCCTTTCTT GGATCAACCC GCTCAATGCC TGGAGATTTG GGCGTGCCCC CG -#CGAGACTG 240 - - CTAGCCGAGT AGTGTTGGGT CGCGAAAGGC CTTGTGGTAC TGCCTGATAG GG -#TGCTTGCG 300 - - AGTGCCCCGG GAGGTCTCGT AGACCGTGCA CC ATG AGC ACG AAT - # CCT AAACCT 353 - # - #Met Ser Thr Asn Pro Lys Pro - # - # 1 5 - - CAA AGA AAA ACC AAA CGT AAC ACC AAC CGC CG - #C CCA CAG GAC GTC AAG 401 Gln Arg Lys Thr Lys Arg Asn Thr Asn Arg Ar - #g Pro Gln Asp Val Lys 10 - # 15 - # 20 - - TTC CCG GGC GGT GGT CAG ATC GTT GGT GGA GT - #T TAC CTG TTG CCG CGC 449 Phe Pro Gly Gly Gly Gln Ile Val Gly Gly Va - #l Tyr Leu Leu Pro Arg 25 - # 30 - # 35 - - AGG GGC CCC AGG TTG GGT GTG CGC GCG CCC AG - #G AAG ACT TCC GAG CGG 497 Arg Gly Pro Arg Leu Gly Val Arg Ala Pro Ar - #g Lys Thr Ser Glu Arg 40 - # 45 - # 50 - # 55 - - TCG CAA CCT CGT GGA AGG CGA CAA CCT ATC CC - #C AAG GCT CGC CGG CCC 545 Ser Gln Pro Arg Gly Arg Arg Gln Pro Ile Pr - #o Lys Ala Arg Arg Pro 60 - # 65 - # 70 - - GAG GGC AGG ACC TGG GCT CAG CCC GGG TAC CC - #T TGG CCT CTC TAT GGC 593 Glu Gly Arg Thr Trp Ala Gln Pro Gly Tyr Pr - #o Trp Pro Leu Tyr Gly 75 - # 80 - # 85 - - AAT GAG GGC TTA GGG TGG GCA GGA TGG CTC CT - #G TCA CCC CGC GGC TCC 641 Asn Glu Gly Leu Gly Trp Ala Gly Trp Leu Le - #u Ser Pro Arg Gly Ser 90 - # 95 - # 100 - - CGG CCT AGT TGG GGC CCC ACG GAC CCC CGG CG - #T AGG TCG CGT AAT TTG 689 Arg Pro Ser Trp Gly Pro Thr Asp Pro Arg Ar - #g Arg Ser Arg Asn Leu 105 - # 110 - # 115 - - GGT AAG GTC ATC GAT ACC CTC ACA TGC GGC TT - #C GCC GAT CTC ATG GGG 737 Gly Lys Val Ile Asp Thr Leu Thr Cys Gly Ph - #e Ala Asp Leu Met Gly 120 1 - #25 1 - #30 1 -#35 - - TAC ATT CCG CTC GTC GGC GCC CCC CTG GGG GG - #C GCT GCC AGG GCCCTG 785 Tyr Ile Pro Leu Val Gly Ala Pro Leu Gly Gl - #y Ala Ala Arg Ala Leu 140 - # 145 - # 150 - - GCA CAT GGT GTC CGG GTT CTG GAG GAC GGC GT - #G AAC TAT GCA ACA GGG 833 Ala His Gly Val Arg Val Leu Glu Asp Gly Va - #l Asn Tyr Ala Thr Gly 155 - # 160 - # 165 - - AAT CTG CCC GGT TGC TCT TTT TCT ATC TTC CT - #C TTG GCT CTG CTG TCC 881 Asn Leu Pro Gly Cys Ser Phe Ser Ile Phe Le - #u Leu Ala Leu Leu Ser 170 - # 175 - # 180 - - TGC CTG ACC ACC CCA GCT TCC GCT TAC GAA GT - #G CAC AAC GTG TCC GGG 929 Cys Leu Thr Thr Pro Ala Ser Ala Tyr Glu Va - #l His Asn Val Ser Gly 185 - # 190 - # 195 - - ATA TAT CAT GTC ACG AAC GAC TGC TCC AAC GC - #A AGC ATT GTG TAT GAG 977 Ile Tyr His Val Thr Asn Asp Cys Ser Asn Al - #a Ser Ile Val Tyr Glu 200 2 - #05 2 - #10 2 -#15 - - GCA GCG GAC TTG ATC ATG CAT ACT CCT GGG TG - #C GTG CCC TGC GTTCGG 1025 Ala Ala Asp Leu Ile Met His Thr Pro Gly Cy - #s Val Pro Cys Val Arg 220 - # 225 - # 230 - - GAA GGC AAC TCC TCC CGC TGC TGG GTA GCG CT - #C ACT CCC ACG CTC GCA 1073 Glu Gly Asn Ser Ser Arg Cys Trp Val Ala Le - #u Thr Pro Thr Leu Ala 235 - # 240 - # 245 - - GCC AGG AAC GTC ACC ATC CCC ACC ACG ACG AT - #A CGA CGC CAC GTC GAT 1121 Ala Arg Asn Val Thr Ile Pro Thr Thr Thr Il - #e Arg Arg His Val Asp 250 - # 255 - # 260 - - CTG CTC GTT GGG GCG GCT GCT TTC TGT TCC GC - #T ATG TAC GTG GGG GAC 1169 Leu Leu Val Gly Ala Ala Ala Phe Cys Ser Al - #a Met Tyr Val Gly Asp 265 - # 270 - # 275 - - CTC TGC GGA TCT GTT TTC CTC GTC TCT CAG CT - #G TTC ACC TTC TCG CCT 1217 Leu Cys Gly Ser Val Phe Leu Val Ser Gln Le - #u Phe Thr Phe Ser Pro 280 2 - #85 2 - #90 2 -#95 - - CGC CGG CAT GTG ACA TTA CAG GAC TGT AAC TG - #C TCA ATT TAT CCCGGC 1265 Arg Arg His Val Thr Leu Gln Asp Cys Asn Cy - #s Ser Ile Tyr Pro Gly 300 - # 305 - # 310 - - CAT GTG TCG GGT CAC CGT ATG GCT TGG GAC AT - #G ATG ATG AAC TGG TCG 1313 His Val Ser Gly His Arg Met Ala Trp Asp Me - #t Met Met Asn Trp Ser 315 - # 320 - # 325 - - CCC ACA ACA GCC CTA GTG GTG TCG CAG TTA CT - #C CGG ATC CCA CAA GCC 1361 Pro Thr Thr Ala Leu Val Val Ser Gln Leu Le - #u Arg Ile Pro Gln Ala 330 - # 335 - # 340 - - GTC GTG GAC ATG GTG GCG GGG GCC CAC TGG GG - #A GTC CTG GCG GGC CTT 1409 Val Val Asp Met Val Ala Gly Ala His Trp Gl - #y Val Leu Ala Gly Leu 345 - # 350 - # 355 - - GCC TAC TAT TCC ATG GCG GGG AAC TGG GCT AA - #G GTT CTG ATT GTG ATG 1457 Ala Tyr Tyr Ser Met Ala Gly Asn Trp Ala Ly - #s Val Leu Ile Val Met 360 3 - #65 3 - #70 3 -#75 - - CTA CTT TTT GCT GGC GTT GAC GGG GAT ACC CA - #C GTG ACA GGG - #1499 Leu Leu Phe Ala Gly Val Asp Gly Asp Thr Hi - #s Val Thr Gly 380 - # 385 - - - - (2) INFORMATION FOR SEQ ID NO:4: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 389 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4: - - Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Th - #r Lys Arg Asn Thr Asn 1 5 - # 10 - # 15 - - Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gl - #y Gly Gln Ile Val Gly 20 - # 25 - # 30 - - Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Ar - #g Leu Gly Val Arg Ala 35 - # 40 - # 45 - - Pro Arg Lys Thr Ser Glu Arg Ser Gln Pro Ar - #g Gly Arg Arg Gln Pro 50 - # 55 - # 60 - - Ile Pro Lys Ala Arg Arg Pro Glu Gly Arg Th - #r Trp Ala Gln Pro Gly 65 - # 70 - # 75 - # 80 - - Tyr Pro Trp Pro Leu Tyr Gly Asn Glu Gly Le - #u Gly Trp Ala Gly Trp 85 - # 90 - # 95 - - Leu Leu Ser Pro Arg Gly Ser Arg Pro Ser Tr - #p Gly Pro Thr Asp Pro 100 - # 105 - # 110 - - Arg Arg Arg Ser Arg Asn Leu Gly Lys Val Il - #e Asp Thr Leu Thr Cys 115 - # 120 - # 125 - - Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Le - #u Val Gly Ala Pro Leu 130 - # 135 - # 140 - - Gly Gly Ala Ala Arg Ala Leu Ala His Gly Va - #l Arg Val Leu Glu Asp 145 1 - #50 1 - #55 1 -#60 - - Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gl - #y Cys Ser Phe SerIle 165 - # 170 - # 175 - - Phe Leu Leu Ala Leu Leu Ser Cys Leu Thr Th - #r Pro Ala Ser Ala Tyr 180 - # 185 - # 190 - - Glu Val His Asn Val Ser Gly Ile Tyr His Va - #l Thr Asn Asp Cys Ser 195 - # 200 - # 205 - - Asn Ala Ser Ile Val Tyr Glu Ala Ala Asp Le - #u Ile Met His Thr Pro 210 - # 215 - # 220 - - Gly Cys Val Pro Cys Val Arg Glu Gly Asn Se - #r Ser Arg Cys Trp Val 225 2 - #30 2 - #35 2 -#40 - - Ala Leu Thr Pro Thr Leu Ala Ala Arg Asn Va - #l Thr Ile Pro ThrThr 245 - # 250 - # 255 - - Thr Ile Arg Arg His Val Asp Leu Leu Val Gl - #y Ala Ala Ala Phe Cys 260 - # 265 - # 270 - - Ser Ala Met Tyr Val Gly Asp Leu Cys Gly Se - #r Val Phe Leu Val Ser 275 - # 280 - # 285 - - Gln Leu Phe Thr Phe Ser Pro Arg Arg His Va - #l Thr Leu Gln Asp Cys 290 - # 295 - # 300 - - Asn Cys Ser Ile Tyr Pro Gly His Val Ser Gl - #y His Arg Met Ala Trp 305 3 - #10 3 - #15 3 -#20 - - Asp Met Met Met Asn Trp Ser Pro Thr Thr Al - #a Leu Val Val SerGln 325 - # 330 - # 335 - - Leu Leu Arg Ile Pro Gln Ala Val Val Asp Me - #t Val Ala Gly Ala His 340 - # 345 - # 350 - - Trp Gly Val Leu Ala Gly Leu Ala Tyr Tyr Se - #r Met Ala Gly Asn Trp 355 - # 360 - # 365 - - Ala Lys Val Leu Ile Val Met Leu Leu Phe Al - #a Gly Val Asp Gly Asp 370 - # 375 - # 380 - - Thr His Val Thr Gly 385 - - - - (2) INFORMATION FOR SEQ ID NO:5: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 90 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..90 (D) OTHER INFORMATION: - #/note: "sequence = 333 - 422 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..90 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: - - ATG AGC ACG AAT CCT AAA CCT CAA AGA AAA AC - #C AAA CGT AAC ACC AAC 48 Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Th - #r Lys Arg Asn Thr Asn 1 5 - # 10 - # 15 - - CGC CGC CCA CAG GAC GTC AAG TTC CCG GGC GG - #T GGT CAG ATC - # 90 Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gl - #y Gly Gln Ile 20 - # 25 - # 30 - - - - (2) INFORMATION FOR SEQ ID NO:6: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 30 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: - - Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Th - #r Lys Arg Asn Thr Asn 1 5 - # 10 - # 15 - - Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gl - #y Gly Gln Ile 20 - # 25 - # 30 - - - - (2) INFORMATION FOR SEQ ID NO:7: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 345 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..345 (D) OTHER INFORMATION: - #/note: "sequence = 333 - 677 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..345 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7: - - ATG AGC ACG AAT CCT AAA CCT CAA AGA AAA AC - #C AAA CGT AAC ACC AAC 48 Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Th - #r Lys Arg Asn Thr Asn 1 5 - # 10 - # 15 - - CGC CGC CCA CAG GAC GTC AAG TTC CCG GGC GG - #T GGT CAG ATC GTT GGT 96 Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gl - #y Gly Gln Ile Val Gly 20 - # 25 - # 30 - - GGA GTT TAC CTG TTG CCG CGC AGG GGC CCC AG - #G TTG GGT GTG CGC GCG 144 Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Ar - #g Leu Gly Val Arg Ala 35 - # 40 - # 45 - - CCC AGG AAG ACT TCC GAG CGG TCG CAA CCT CG - #T GGA AGG CGA CAA CCT 192 Pro Arg Lys Thr Ser Glu Arg Ser Gln Pro Ar - #g Gly Arg Arg Gln Pro 50 - # 55 - # 60 - - ATC CCC AAG GCT CGC CGG CCC GAG GGC AGG AC - #C TGG GCT CAG CCC GGG 240 Ile Pro Lys Ala Arg Arg Pro Glu Gly Arg Th - #r Trp Ala Gln Pro Gly 65 - # 70 - # 75 - # 80 - - TAC CCT TGG CCT CTC TAT GGC AAT GAG GGC TT - #A GGG TGG GCA GGA TGG 288 Tyr Pro Trp Pro Leu Tyr Gly Asn Glu Gly Le - #u Gly Trp Ala Gly Trp 85 - # 90 - # 95 - - CTC CTG TCA CCC CGC GGC TCC CGG CCT AGT TG - #G GGC CCC ACG GAC CCC 336 Leu Leu Ser Pro Arg Gly Ser Arg Pro Ser Tr - #p Gly Pro Thr Asp Pro 100 - # 105 - # 110 - - CGG CGT AGG - # - #- # 345 Arg Arg Arg 115 - - - - (2) INFORMATION FOR SEQ ID NO:8: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 115 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: - - Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Th - #r Lys Arg Asn ThrAsn 1 5 - # 10 - # 15 - - Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gl - #y Gly Gln Ile Val Gly 20 - # 25 - # 30 - - Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Ar - #g Leu Gly Val Arg Ala 35 - # 40 - # 45 - - Pro Arg Lys Thr Ser Glu Arg Ser Gln Pro Ar - #g Gly Arg Arg Gln Pro 50 - # 55 - # 60 - - Ile Pro Lys Ala Arg Arg Pro Glu Gly Arg Th - #r Trp Ala Gln Pro Gly 65 - # 70 - # 75 - # 80 - - Tyr Pro Trp Pro Leu Tyr Gly Asn Glu Gly Le - #u Gly Trp Ala Gly Trp 85 - # 90 - # 95 - - Leu Leu Ser Pro Arg Gly Ser Arg Pro Ser Tr - #p Gly Pro Thr Asp Pro 100 - # 105 - # 110 - - Arg Arg Arg 115 - - - - (2) INFORMATION FOR SEQ ID NO:9: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1167 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..1167 (D) OTHER INFORMATION: - #/note: "sequence = 333 - 1499 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..1167 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: - - ATG AGC ACG AAT CCT AAA CCT CAA AGA AAA AC - #C AAA CGT AAC ACC AAC 48 Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Th - #r Lys Arg Asn Thr Asn 1 5 - # 10 - # 15 - - CGC CGC CCA CAG GAC GTC AAG TTC CCG GGC GG - #T GGT CAG ATC GTT GGT 96 Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gl - #y Gly Gln Ile Val Gly 20 - # 25 - # 30 - - GGA GTT TAC CTG TTG CCG CGC AGG GGC CCC AG - #G TTG GGT GTG CGC GCG 144 Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Ar - #g Leu Gly Val Arg Ala 35 - # 40 - # 45 - - CCC AGG AAG ACT TCC GAG CGG TCG CAA CCT CG - #T GGA AGG CGA CAA CCT 192 Pro Arg Lys Thr Ser Glu Arg Ser Gln Pro Ar - #g Gly Arg Arg Gln Pro 50 - # 55 - # 60 - - ATC CCC AAG GCT CGC CGG CCC GAG GGC AGG AC - #C TGG GCT CAG CCC GGG 240 Ile Pro Lys Ala Arg Arg Pro Glu Gly Arg Th - #r Trp Ala Gln Pro Gly 65 - # 70 - # 75 - # 80 - - TAC CCT TGG CCT CTC TAT GGC AAT GAG GGC TT - #A GGG TGG GCA GGA TGG 288 Tyr Pro Trp Pro Leu Tyr Gly Asn Glu Gly Le - #u Gly Trp Ala Gly Trp 85 - # 90 - # 95 - - CTC CTG TCA CCC CGC GGC TCC CGG CCT AGT TG - #G GGC CCC ACG GAC CCC 336 Leu Leu Ser Pro Arg Gly Ser Arg Pro Ser Tr - #p Gly Pro Thr Asp Pro 100 - # 105 - # 110 - - CGG CGT AGG TCG CGT AAT TTG GGT AAG GTC AT - #C GAT ACC CTC ACA TGC 384 Arg Arg Arg Ser Arg Asn Leu Gly Lys Val Il - #e Asp Thr Leu Thr Cys 115 - # 120 - # 125 - - GGC TTC GCC GAT CTC ATG GGG TAC ATT CCG CT - #C GTC GGC GCC CCC CTG 432 Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Le - #u Val Gly Ala Pro Leu 130 - # 135 - # 140 - - GGG GGC GCT GCC AGG GCC CTG GCA CAT GGT GT - #C CGG GTT CTG GAG GAC 480 Gly Gly Ala Ala Arg Ala Leu Ala His Gly Va - #l Arg Val Leu Glu Asp 145 1 - #50 1 - #55 1 -#60 - - GGC GTG AAC TAT GCA ACA GGG AAT CTG CCC GG - #T TGC TCT TTT TCTATC 528 Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gl - #y Cys Ser Phe Ser Ile 165 - # 170 - # 175 - - TTC CTC TTG GCT CTG CTG TCC TGC CTG ACC AC - #C CCA GCT TCC GCT TAC 576 Phe Leu Leu Ala Leu Leu Ser Cys Leu Thr Th - #r Pro Ala Ser Ala Tyr 180 - # 185 - # 190 - - GAA GTG CAC AAC GTG TCC GGG ATA TAT CAT GT - #C ACG AAC GAC TGC TCC 624 Glu Val His Asn Val Ser Gly Ile Tyr His Va - #l Thr Asn Asp Cys Ser 195 - # 200 - # 205 - - AAC GCA AGC ATT GTG TAT GAG GCA GCG GAC TT - #G ATC ATG CAT ACT CCT 672 Asn Ala Ser Ile Val Tyr Glu Ala Ala Asp Le - #u Ile Met His Thr Pro 210 - # 215 - # 220 - - GGG TGC GTG CCC TGC GTT CGG GAA GGC AAC TC - #C TCC CGC TGC TGG GTA 720 Gly Cys Val Pro Cys Val Arg Glu Gly Asn Se - #r Ser Arg Cys Trp Val 225 2 - #30 2 - #35 2 -#40 - - GCG CTC ACT CCC ACG CTC GCA GCC AGG AAC GT - #C ACC ATC CCC ACCACG 768 Ala Leu Thr Pro Thr Leu Ala Ala Arg Asn Va - #l Thr Ile Pro Thr Thr 245 - # 250 - # 255 - - ACG ATA CGA CGC CAC GTC GAT CTG CTC GTT GG - #G GCG GCT GCT TTC TGT 816 Thr Ile Arg Arg His Val Asp Leu Leu Val Gl - #y Ala Ala Ala Phe Cys 260 - # 265 - # 270 - - TCC GCT ATG TAC GTG GGG GAC CTC TGC GGA TC - #T GTT TTC CTC GTC TCT 864 Ser Ala Met Tyr Val Gly Asp Leu Cys Gly Se - #r Val Phe Leu Val Ser 275 - # 280 - # 285 - - CAG CTG TTC ACC TTC TCG CCT CGC CGG CAT GT - #G ACA TTA CAG GAC TGT 912 Gln Leu Phe Thr Phe Ser Pro Arg Arg His Va - #l Thr Leu Gln Asp Cys 290 - # 295 - # 300 - - AAC TGC TCA ATT TAT CCC GGC CAT GTG TCG GG - #T CAC CGT ATG GCT TGG 960 Asn Cys Ser Ile Tyr Pro Gly His Val Ser Gl - #y His Arg Met Ala Trp 305 3 - #10 3 - #15 3 -#20 - - GAC ATG ATG ATG AAC TGG TCG CCC ACA ACA GC - #C CTA GTG GTG TCGCAG 1008 Asp Met Met Met Asn Trp Ser Pro Thr Thr Al - #a Leu Val Val Ser Gln 325 - # 330 - # 335 - - TTA CTC CGG ATC CCA CAA GCC GTC GTG GAC AT - #G GTG GCG GGG GCC CAC 1056 Leu Leu Arg Ile Pro Gln Ala Val Val Asp Me - #t Val Ala Gly Ala His 340 - # 345 - # 350 - - TGG GGA GTC CTG GCG GGC CTT GCC TAC TAT TC - #C ATG GCG GGG AAC TGG 1104 Trp Gly Val Leu Ala Gly Leu Ala Tyr Tyr Se - #r Met Ala Gly Asn Trp 355 - # 360 - # 365 - - GCT AAG GTT CTG ATT GTG ATG CTA CTT TTT GC - #T GGC GTT GAC GGG GAT 1152 Ala Lys Val Leu Ile Val Met Leu Leu Phe Al - #a Gly Val Asp Gly Asp 370 - # 375 - # 380 - - ACC CAC GTG ACA GGG - # - # - # 1167 Thr His Val Thr Gly 385 - - - - (2) INFORMATION FOR SEQ ID NO:10: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 389 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: - - Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Th - #r Lys Arg Asn Thr Asn 1 5 - # 10 - # 15 - - Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gl - #y Gly Gln Ile Val Gly 20 - # 25 - # 30 - - Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Ar - #g Leu Gly Val Arg Ala 35 - # 40 - # 45 - - Pro Arg Lys Thr Ser Glu Arg Ser Gln Pro Ar - #g Gly Arg Arg Gln Pro 50 - # 55 - # 60 - - Ile Pro Lys Ala Arg Arg Pro Glu Gly Arg Th - #r Trp Ala Gln Pro Gly 65 - # 70 - # 75 - # 80 - - Tyr Pro Trp Pro Leu Tyr Gly Asn Glu Gly Le - #u Gly Trp Ala Gly Trp 85 - # 90 - # 95 - - Leu Leu Ser Pro Arg Gly Ser Arg Pro Ser Tr - #p Gly Pro Thr Asp Pro 100 - # 105 - # 110 - - Arg Arg Arg Ser Arg Asn Leu Gly Lys Val Il - #e Asp Thr Leu Thr Cys 115 - # 120 - # 125 - - Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Le - #u Val Gly Ala Pro Leu 130 - # 135 - # 140 - - Gly Gly Ala Ala Arg Ala Leu Ala His Gly Va - #l Arg Val Leu Glu Asp 145 1 - #50 1 - #55 1 -#60 - - Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gl - #y Cys Ser Phe SerIle 165 - # 170 - # 175 - - Phe Leu Leu Ala Leu Leu Ser Cys Leu Thr Th - #r Pro Ala Ser Ala Tyr 180 - # 185 - # 190 - - Glu Val His Asn Val Ser Gly Ile Tyr His Va - #l Thr Asn Asp Cys Ser 195 - # 200 - # 205 - - Asn Ala Ser Ile Val Tyr Glu Ala Ala Asp Le - #u Ile Met His Thr Pro 210 - # 215 - # 220 - - Gly Cys Val Pro Cys Val Arg Glu Gly Asn Se - #r Ser Arg Cys Trp Val 225 2 - #30 2 - #35 2 -#40 - - Ala Leu Thr Pro Thr Leu Ala Ala Arg Asn Va - #l Thr Ile Pro ThrThr 245 - # 250 - # 255 - - Thr Ile Arg Arg His Val Asp Leu Leu Val Gl - #y Ala Ala Ala Phe Cys 260 - # 265 - # 270 - - Ser Ala Met Tyr Val Gly Asp Leu Cys Gly Se - #r Val Phe Leu Val Ser 275 - # 280 - # 285 - - Gln Leu Phe Thr Phe Ser Pro Arg Arg His Va - #l Thr Leu Gln Asp Cys 290 - # 295 - # 300 - - Asn Cys Ser Ile Tyr Pro Gly His Val Ser Gl - #y His Arg Met Ala Trp 305 3 - #10 3 - #15 3 -#20 - - Asp Met Met Met Asn Trp Ser Pro Thr Thr Al - #a Leu Val Val SerGln 325 - # 330 - # 335 - - Leu Leu Arg Ile Pro Gln Ala Val Val Asp Me - #t Val Ala Gly Ala His 340 - # 345 - # 350 - - Trp Gly Val Leu Ala Gly Leu Ala Tyr Tyr Se - #r Met Ala Gly Asn Trp 355 - # 360 - # 365 - - Ala Lys Val Leu Ile Val Met Leu Leu Phe Al - #a Gly Val Asp Gly Asp 370 - # 375 - # 380 - - Thr His Val Thr Gly 385 - - - - (2) INFORMATION FOR SEQ ID NO:11: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 6039 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..6039 (D) OTHER INFORMATION: - #/note: "sequence = 333 - 6371 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..6039 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11: - - ATG AGC ACG AAT CCT AAA CCT CAA AGA AAA AC - #C AAA CGT AAC ACC AAC 48 Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Th - #r Lys Arg Asn Thr Asn 1 5 - # 10 - # 15 - - CGC CGC CCA CAG GAC GTC AAG TTC CCG GGC GG - #T GGT CAG ATC GTT GGT 96 Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gl - #y Gly Gln Ile Val Gly 20 - # 25 - # 30 - - GGA GTT TAC CTG TTG CCG CGC AGG GGC CCC AG - #G TTG GGT GTG CGC GCG 144 Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Ar - #g Leu Gly Val Arg Ala 35 - # 40 - # 45 - - CCC AGG AAG ACT TCC GAG CGG TCG CAA CCT CG - #T GGA AGG CGA CAA CCT 192 Pro Arg Lys Thr Ser Glu Arg Ser Gln Pro Ar - #g Gly Arg Arg Gln Pro 50 - # 55 - # 60 - - ATC CCC AAG GCT CGC CGG CCC GAG GGC AGG AC - #C TGG GCT CAG CCC GGG 240 Ile Pro Lys Ala Arg Arg Pro Glu Gly Arg Th - #r Trp Ala Gln Pro Gly 65 - # 70 - # 75 - # 80 - - TAC CCT TGG CCT CTC TAT GGC AAT GAG GGC TT - #A GGG TGG GCA GGA TGG 288 Tyr Pro Trp Pro Leu Tyr Gly Asn Glu Gly Le - #u Gly Trp Ala Gly Trp 85 - # 90 - # 95 - - CTC CTG TCA CCC CGC GGC TCC CGG CCT AGT TG - #G GGC CCC ACG GAC CCC 336 Leu Leu Ser Pro Arg Gly Ser Arg Pro Ser Tr - #p Gly Pro Thr Asp Pro 100 - # 105 - # 110 - - CGG CGT AGG TCG CGT AAT TTG GGT AAG GTC AT - #C GAT ACC CTC ACA TGC 384 Arg Arg Arg Ser Arg Asn Leu Gly Lys Val Il - #e Asp Thr Leu Thr Cys 115 - # 120 - # 125 - - GGC TTC GCC GAT CTC ATG GGG TAC ATT CCG CT - #C GTC GGC GCC CCC CTG 432 Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Le - #u Val Gly Ala Pro Leu 130 - # 135 - # 140 - - GGG GGC GCT GCC AGG GCC CTG GCA CAT GGT GT - #C CGG GTT CTG GAG GAC 480 Gly Gly Ala Ala Arg Ala Leu Ala His Gly Va - #l Arg Val Leu Glu Asp 145 1 - #50 1 - #55 1 -#60 - - GGC GTG AAC TAT GCA ACA GGG AAT CTG CCC GG - #T TGC TCT TTT TCTATC 528 Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gl - #y Cys Ser Phe Ser Ile 165 - # 170 - # 175 - - TTC CTC TTG GCT CTG CTG TCC TGC CTG ACC AC - #C CCA GCT TCC GCT TAC 576 Phe Leu Leu Ala Leu Leu Ser Cys Leu Thr Th - #r Pro Ala Ser Ala Tyr 180 - # 185 - # 190 - - GAA GTG CAC AAC GTG TCC GGG ATA TAT CAT GT - #C ACG AAC GAC TGC TCC 624 Glu Val His Asn Val Ser Gly Ile Tyr His Va - #l Thr Asn Asp Cys Ser 195 - # 200 - # 205 - - AAC GCA AGC ATT GTG TAT GAG GCA GCG GAC TT - #G ATC ATG CAT ACT CCT 672 Asn Ala Ser Ile Val Tyr Glu Ala Ala Asp Le - #u Ile Met His Thr Pro 210 - # 215 - # 220 - - GGG TGC GTG CCC TGC GTT CGG GAA GGC AAC TC - #C TCC CGC TGC TGG GTA 720 Gly Cys Val Pro Cys Val Arg Glu Gly Asn Se - #r Ser Arg Cys Trp Val 225 2 - #30 2 - #35 2 -#40 - - GCG CTC ACT CCC ACG CTC GCA GCC AGG AAC GT - #C ACC ATC CCC ACCACG 768 Ala Leu Thr Pro Thr Leu Ala Ala Arg Asn Va - #l Thr Ile Pro Thr Thr 245 - # 250 - # 255 - - ACG ATA CGA CGC CAC GTC GAT CTG CTC GTT GG - #G GCG GCT GCT TTC TGT 816 Thr Ile Arg Arg His Val Asp Leu Leu Val Gl - #y Ala Ala Ala Phe Cys 260 - # 265 - # 270 - - TCC GCT ATG TAC GTG GGG GAC CTC TGC GGA TC - #T GTT TTC CTC GTC TCT 864 Ser Ala Met Tyr Val Gly Asp Leu Cys Gly Se - #r Val Phe Leu Val Ser 275 - # 280 - # 285 - - CAG CTG TTC ACC TTC TCG CCT CGC CGG CAT GT - #G ACA TTA CAG GAC TGT 912 Gln Leu Phe Thr Phe Ser Pro Arg Arg His Va - #l Thr Leu Gln Asp Cys 290 - # 295 - # 300 - - AAC TGC TCA ATT TAT CCC GGC CAT GTG TCG GG - #T CAC CGT ATG GCT TGG 960 Asn Cys Ser Ile Tyr Pro Gly His Val Ser Gl - #y His Arg Met Ala Trp 305 3 - #10 3 - #15 3 -#20 - - GAC ATG ATG ATG AAC TGG TCG CCC ACA ACA GC - #C CTA GTG GTG TCGCAG 1008 Asp Met Met Met Asn Trp Ser Pro Thr Thr Al - #a Leu Val Val Ser Gln 325 - # 330 - # 335 - - TTA CTC CGG ATC CCA CAA GCC GTC GTG GAC AT - #G GTG GCG GGG GCC CAC 1056 Leu Leu Arg Ile Pro Gln Ala Val Val Asp Me - #t Val Ala Gly Ala His 340 - # 345 - # 350 - - TGG GGA GTC CTG GCG GGC CTT GCC TAC TAT TC - #C ATG GCG GGG AAC TGG 1104 Trp Gly Val Leu Ala Gly Leu Ala Tyr Tyr Se - #r Met Ala Gly Asn Trp 355 - # 360 - # 365 - - GCT AAG GTT CTG ATT GTG ATG CTA CTT TTT GC - #T GGC GTT GAC GGG GAT 1152 Ala Lys Val Leu Ile Val Met Leu Leu Phe Al - #a Gly Val Asp Gly Asp 370 - # 375 - # 380 - - ACC CAC GTG ACA GGG GGG GCG CAA GCC AAA AC - #C ACC AAC AGG CTC GTG 1200 Thr His Val Thr Gly Gly Ala Gln Ala Lys Th - #r Thr Asn Arg Leu Val 385 3 - #90 3 - #95 4 -#00 - - TCC ATG TTC GCA AGT GGG CCG TCT CAG AAA AT - #C CAG CTT ATA AACACC 1248 Ser Met Phe Ala Ser Gly Pro Ser Gln Lys Il - #e Gln Leu Ile Asn Thr 405 - # 410 - # 415 - - AAT GGG AGT TGG CAC ATC AAC AGG ACT GCC CT - #G AAC TGC AAT GAC TCT 1296 Asn Gly Ser Trp His Ile Asn Arg Thr Ala Le - #u Asn Cys Asn Asp Ser 420 - # 425 - # 430 - - CTC CAG ACT GGG TTT CTT GCC GCG CTG TTC TA - #C ACA CAT AGT TTC AAC 1344 Leu Gln Thr Gly Phe Leu Ala Ala Leu Phe Ty - #r Thr His Ser Phe Asn 435 - # 440 - # 445 - - TCG TCC GGG TGC CCA GAG CGC ATG GCC CAG TG - #C CGC ACC ATT GAC AAG 1392 Ser Ser Gly Cys Pro Glu Arg Met Ala Gln Cy - #s Arg Thr Ile Asp Lys 450 - # 455 - # 460 - - TTC GAC CAG GGA TGG GGT CCC ATT ACT TAT GC - #T GAG TCT AGC AGA TCA 1440 Phe Asp Gln Gly Trp Gly Pro Ile Thr Tyr Al - #a Glu Ser Ser Arg Ser 465 4 - #70 4 - #75 4 -#80 - - GAC CAG AGG CCA TAT TGC TGG CAC TAC CCA CC - #T CCA CAA TGT ACCATC 1488 Asp Gln Arg Pro Tyr Cys Trp His Tyr Pro Pr - #o Pro Gln Cys Thr Ile 485 - # 490 - # 495 - - GTA CCT GCG TCG GAG GTG TGC GGC CCA GTG TA - #C TGC TTC ACC CCA AGC 1536 Val Pro Ala Ser Glu Val Cys Gly Pro Val Ty - #r Cys Phe Thr Pro Ser 500 - # 505 - # 510 - - CCT GTC GTC GTG GGG ACG ACC GAT CGT TTC GG - #T GTC CCT ACG TAT AGA 1584 Pro Val Val Val Gly Thr Thr Asp Arg Phe Gl - #y Val Pro Thr Tyr Arg 515 - # 520 - # 525 - - TGG GGG GAG AAC GAG ACT GAC GTG CTG CTG CT - #C AAC AAC ACG CGG CCG 1632 Trp Gly Glu Asn Glu Thr Asp Val Leu Leu Le - #u Asn Asn Thr Arg Pro 530 - # 535 - # 540 - - CCG CAA GGC AAC TGG TTC GGC TGC ACA TGG AT - #G AAT AGC ACC GGG TTC 1680 Pro Gln Gly Asn Trp Phe Gly Cys Thr Trp Me - #t Asn Ser Thr Gly Phe 545 5 - #50 5 - #55 5 -#60 - - ACC AAG ACA TGT GGG GGG CCC CCG TGT AAC AT - #C GGG GGG GTC GGCAAC 1728 Thr Lys Thr Cys Gly Gly Pro Pro Cys Asn Il - #e Gly Gly Val Gly Asn 565 - # 570 - # 575 - - AAC ACC CTG ACC TGC CCC ACG GAC TGC TTC CG - #G AAG CAC CCC GAG GCT 1776 Asn Thr Leu Thr Cys Pro Thr Asp Cys Phe Ar - #g Lys His Pro Glu Ala 580 - # 585 - # 590 - - ACC TAC ACA AAA TGT GGT TCG GGG CCT TGG CT - #G ACA CCT AGG TGC ATG 1824 Thr Tyr Thr Lys Cys Gly Ser Gly Pro Trp Le - #u Thr Pro Arg Cys Met 595 - # 600 - # 605 - - GTT GAC TAT CCA TAC AGG CTC TGG CAT TAC CC - #C TGC ACT GTT AAC TTT 1872 Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pr - #o Cys Thr Val Asn Phe 610 - # 615 - # 620 - - ACC ATC TTC AAG GTT AGG ATG TAT GTG GGG GG - #G GTG GAG CAC AGG CTC 1920 Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gl - #y Val Glu His Arg Leu 625 6 - #30 6 - #35 6 -#40 - - AAT GCT GCA TGC AAT TGG ACC CGA GGA GAG CG - #T TGT GAC TTG GAGGAC 1968 Asn Ala Ala Cys Asn Trp Thr Arg Gly Glu Ar - #g Cys Asp Leu Glu Asp 645 - # 650 - # 655 - - AGG GAT AGG CCG GAG CTC AGC CCG CTG CTG CT - #G TCT ACA ACA GAG TGG 2016 Arg Asp Arg Pro Glu Leu Ser Pro Leu Leu Le - #u Ser Thr Thr Glu Trp 660 - # 665 - # 670 - - CAG GTA CTG CCC TGT TCC TTC ACC ACC CTA CC - #A GCT CTG TCC ACT GGC 2064 Gln Val Leu Pro Cys Ser Phe Thr Thr Leu Pr - #o Ala Leu Ser Thr Gly 675 - # 680 - # 685 - - TTG ATT CAC CTC CAT CAG AAC ATC GTG GAC GT - #G CAA TAC CTA TAC GGT 2112 Leu Ile His Leu His Gln Asn Ile Val Asp Va - #l Gln Tyr Leu Tyr Gly 690 - # 695 - # 700 - - ATA GGG TCA GCG GTT GTC TCC TTT GCA ATC AA - #A TGG GAG TAT GTC CTG 2160 Ile Gly Ser Ala Val Val Ser Phe Ala Ile Ly - #s Trp Glu Tyr Val Leu 705 7 - #10 7 - #15 7 -#20 - - TTG CTT TTC CTT CTC CTA GCG GAC GCA CGT GT - #C TGT GCC TGC TTGTGG 2208 Leu Leu Phe Leu Leu Leu Ala Asp Ala Arg Va - #l Cys Ala Cys Leu Trp 725 - # 730 - # 735 - - ATG ATG CTG CTG ATA GCC CAG GCC GAG GCC GC - #C TTG GAG AAC CTG GTG 2256 Met Met Leu Leu Ile Ala Gln Ala Glu Ala Al - #a Leu Glu Asn Leu Val 740 - # 745 - # 750 - - GTC CTC AAT TCG GCG TCT GTG GCC GGC GCA CA - #T GGC ATC CTC TCC TTC 2304 Val Leu Asn Ser Ala Ser Val Ala Gly Ala Hi - #s Gly Ile Leu Ser Phe 755 - # 760 - # 765 - - CTT GTG TTC TTC TGT GCC GCC TGG TAC ATC AA - #A GGC AGG CTG GTC CCT 2352 Leu Val Phe Phe Cys Ala Ala Trp Tyr Ile Ly - #s Gly Arg Leu Val Pro 770 - # 775 - # 780 - - GGG GCG ACA TAT GCT CTT TAT GGC GTG TGG CC - #G CTG CTC CTG CTC TTG 2400 Gly Ala Thr Tyr Ala Leu Tyr Gly Val Trp Pr - #o Leu Leu Leu Leu Leu 785 7 - #90 7 - #95 8 -#00 - - CTG GCA TTA CCA CCG CGA GCT TAC GCC ATG GA - #C CGG GAG ATG GCTGCA 2448 Leu Ala Leu Pro Pro Arg Ala Tyr Ala Met As - #p Arg Glu Met Ala Ala 805 - # 810 - # 815 - - TCG TGC GGA GGC GCG GTT TTT GTG GGT CTG GT - #A CTC CTG ACT TTG TCA 2496 Ser Cys Gly Gly Ala Val Phe Val Gly Leu Va - #l Leu Leu Thr Leu Ser 820 - # 825 - # 830 - - CCA TAC TAC AAG GTG TTC CTC GCT AGG CTC AT - #A TGG TGG TTA CAA TAT 2544 Pro Tyr Tyr Lys Val Phe Leu Ala Arg Leu Il - #e Trp Trp Leu Gln Tyr 835 - # 840 - # 845 - - TTT ACC ACC AGA GCC GAG GCG GAC TTA CAT GT - #G TGG ATC CCC CCC CTC 2592 Phe Thr Thr Arg Ala Glu Ala Asp Leu His Va - #l Trp Ile Pro Pro Leu 850 - # 855 - # 860 - - AAC GCT CGG GGA GGC CGC GAT GCC ATC ATC CT - #C CTC ATG TGC GCA GTC 2640 Asn Ala Arg Gly Gly Arg Asp Ala Ile Ile Le - #u Leu Met Cys Ala Val 865 8 - #70 8 - #75 8 -#80 - - CAT CCA GAG CTA ATC TTT GAC ATC ACC AAA CT - #T CTA ATT GCC ATACTC 2688 His Pro Glu Leu Ile Phe Asp Ile Thr Lys Le - #u Leu Ile Ala Ile Leu 885 - # 890 - # 895 - - GGT CCG CTC ATG GTG CTC CAA GCT GGC ATA AC - #C AGA GTG CCG TAC TTC 2736 Gly Pro Leu Met Val Leu Gln Ala Gly Ile Th - #r Arg Val Pro Tyr Phe 900 - # 905 - # 910 - - GTG CGC GCT CAA GGG CTC ATT CAT GCA TGC AT - #G TTA GTG CGG AAG GTC 2784 Val Arg Ala Gln Gly Leu Ile His Ala Cys Me - #t Leu Val Arg Lys Val 915 - # 920 - # 925 - - GCT GGG GGT CAT TAT GTC CAA ATG GCC TTC AT - #G AAG CTG GGC GCG CTG 2832 Ala Gly Gly His Tyr Val Gln Met Ala Phe Me - #t Lys Leu Gly Ala Leu 930 - # 935 - # 940 - - ACA GGC ACG TAC ATT TAC AAC CAT CTT ACC CC - #G CTA CGG GAT TGG CCA 2880 Thr Gly Thr Tyr Ile Tyr Asn His Leu Thr Pr - #o Leu Arg Asp Trp Pro 945 9 - #50 9 - #55 9 -#60 - - CGC GCG GGC CTA CGA GAC CTT GCG GTG GCA GT - #G GAG CCC GTC GTCTTC 2928 Arg Ala Gly Leu Arg Asp Leu Ala Val Ala Va - #l Glu Pro Val Val Phe 965 - # 970 - # 975 - - TCC GAC ATG GAG ACC AAG ATC ATC ACC TGG GG - #A GCA GAC ACC GCG GCG 2976 Ser Asp Met Glu Thr Lys Ile Ile Thr Trp Gl - #y Ala Asp Thr Ala Ala 980 - # 985 - # 990 - - TGT GGG GAC ATC ATC TTG GGT CTG CCC GTC TC - #C GCC CGA AGG GGA AAG 3024 Cys Gly Asp Ile Ile Leu Gly Leu Pro Val Se - #r Ala Arg Arg Gly Lys 995 - # 1000 - # 1005 - - GAG ATA CTC CTG GGC CCG GCC GAT AGT CTT GA - #A GGG CGG GGG TTG CGA 3072 Glu Ile Leu Leu Gly Pro Ala Asp Ser Leu Gl - #u Gly Arg Gly Leu Arg 1010 - # 1015 - # 1020 - - CTC CTC GCG CCC ATC ACG GCC TAC TCC CAA CA - #G ACG CGG GGC CTA CTT 3120 Leu Leu Ala Pro Ile Thr Ala Tyr Ser Gln Gl - #n Thr Arg Gly Leu Leu 1025 1030 - # 1035 - # 1040 - - GGT TGC ATC ATC ACT AGC CTT ACA GGC CGG GA - #C AAG AAC CAG GTC GAG 3168 Gly Cys Ile Ile Thr Ser Leu Thr Gly Arg As - #p Lys Asn Gln Val Glu 1045 - # 1050 - # 1055 - - GGA GAG GTT CAG GTG GTT TCC ACC GCA ACA CA - #A TCC TTC CTG GCG ACC 3216 Gly Glu Val Gln Val Val Ser Thr Ala Thr Gl - #n Ser Phe Leu Ala Thr 1060 - # 1065 - # 1070 - - TGC GTC AAC GGC GTG TGT TGG ACC GTT TAC CA - #T GGT GCT GGC TCA AAG 3264 Cys Val Asn Gly Val Cys Trp Thr Val Tyr Hi - #s Gly Ala Gly Ser Lys 1075 - # 1080 - # 1085 - - ACC TTA GCC GCG CCA AAG GGG CCA ATC ACC CA - #G ATG TAC ACT AAT GTG 3312 Thr Leu Ala Ala Pro Lys Gly Pro Ile Thr Gl - #n Met Tyr Thr Asn Val 1090 - # 1095 - # 1100 - - GAC CAG GAC CTC GTC GGC TGG CCC AAG CCC CC - #C GGG GCG CGT TCC TTG 3360 Asp Gln Asp Leu Val Gly Trp Pro Lys Pro Pr - #o Gly Ala Arg Ser Leu 1105 1110 - # 1115 - # 1120 - - ACA CCA TGC ACC TGT GGC AGC TCA GAC CTT TA - #C TTG GTC ACG AGA CAT 3408 Thr Pro Cys Thr Cys Gly Ser Ser Asp Leu Ty - #r Leu Val Thr Arg His 1125 - # 1130 - # 1135 - - GCT GAC GTC ATT CCG GTG CGC CGG CGG GGC GA - #C AGT AGG GGG AGC CTG 3456 Ala Asp Val Ile Pro Val Arg Arg Arg Gly As - #p Ser Arg Gly Ser Leu 1140 - # 1145 - # 1150 - - CTC TCC CCC AGG CCT GTC TCC TAC TTG AAG GG - #C TCT TCG GGT GGT CCA 3504 Leu Ser Pro Arg Pro Val Ser Tyr Leu Lys Gl - #y Ser Ser Gly Gly Pro 1155 - # 1160 - # 1165 - - CTG CTC TGC CCC TTC GGG CAC GCT GTG GGC AT - #C TTC CGG GCT GCC GTA 3552 Leu Leu Cys Pro Phe Gly His Ala Val Gly Il - #e Phe Arg Ala Ala Val 1170 - # 1175 - # 1180 - - TGC ACC CGG GGG GTT GCG AAG GCG GTG GAC TT - #T GTG CCC GTA GAG TCC 3600 Cys Thr Arg Gly Val Ala Lys Ala Val Asp Ph - #e Val Pro Val Glu Ser 1185 1190 - # 1195 - # 1200 - - ATG GAA ACT ACT ATG CGG TCT CCG GTC TTC AC - #G GAC AAC TCA TCC CCC 3648 Met Glu Thr Thr Met Arg Ser Pro Val Phe Th - #r Asp Asn Ser Ser Pro 1205 - # 1210 - # 1215 - - CCG GCC GTA CCG CAG TCA TTT CAA GTG GCC CA - #C CTA CAC GCT CCC ACT 3696 Pro Ala Val Pro Gln Ser Phe Gln Val Ala Hi - #s Leu His Ala Pro Thr 1220 - # 1225 - # 1230 - - GGC AGC GGC AAG AGT ACT AAA GTG CCG GCT GC - #A TAT GCA GCC CAA GGG 3744 Gly Ser Gly Lys Ser Thr Lys Val Pro Ala Al - #a Tyr Ala Ala Gln Gly 1235 - # 1240 - # 1245 - - TAC AAG GTG CTC GTC CTC AAT CCG TCC GTT GC - #C GCT ACC TTA GGG TTT 3792 Tyr Lys Val Leu Val Leu Asn Pro Ser Val Al - #a Ala Thr Leu Gly Phe 1250 - # 1255 - # 1260 - - GGG GCG TAT ATG TCT AAG GCA CAC GGT ATT GA - #C CCC AAC ATC AGA ACT 3840 Gly Ala Tyr Met Ser Lys Ala His Gly Ile As - #p Pro Asn Ile Arg Thr 1265 1270 - # 1275 - # 1280 - - GGG GTA AGG ACC ATT ACC ACA GGC GCC CCC GT - #C ACA TAC TCT ACC TAT 3888 Gly Val Arg Thr Ile Thr Thr Gly Ala Pro Va - #l Thr Tyr Ser Thr Tyr 1285 - # 1290 - # 1295 - - GGC AAG TTT CTT GCC GAT GGT GGT TGC TCT GG - #G GGC GCT TAT GAC ATC 3936 Gly Lys Phe Leu Ala Asp Gly Gly Cys Ser Gl - #y Gly Ala Tyr Asp Ile 1300 - # 1305 - # 1310 - - ATA ATA TGT GAT GAG TGC CAT TCA ACT GAC TC - #G ACT ACA ATC TTG GGC 3984 Ile Ile Cys Asp Glu Cys His Ser Thr Asp Se - #r Thr Thr Ile Leu Gly 1315 - # 1320 - # 1325 - - ATC GGC ACA GTC CTG GAC CAA GCG GAG ACG GC - #T GGA GCG CGG CTT GTC 4032 Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Al - #a Gly Ala Arg Leu Val 1330 - # 1335 - # 1340 - - GTG CTC GCC ACC GCT ACG CCT CCG GGA TCG GT - #C ACC GTG CCA CAC CCA 4080 Val Leu Ala Thr Ala Thr Pro Pro Gly Ser Va - #l Thr Val Pro His Pro 1345 1350 - # 1355 - # 1360 - - AAC ATC GAG GAG GTG GCC CTG TCT AAT ACT GG - #A GAG ATC CCC TTC TAT 4128 Asn Ile Glu Glu Val Ala Leu Ser Asn Thr Gl - #y Glu Ile Pro Phe Tyr 1365 - # 1370 - # 1375 - - GGC AAA GCC ATC CCC ATT GAA GCC ATC AGG GG - #G GGA AGG CAT CTC ATT 4176 Gly Lys Ala Ile Pro Ile Glu Ala Ile Arg Gl - #y Gly Arg His Leu Ile 1380 - # 1385 - # 1390 - - TTC TGT CAT TCC AAG AAG AAG TGC GAC GAG CT - #C GCC GCA AAG CTG TCA 4224 Phe Cys His Ser Lys Lys Lys Cys Asp Glu Le - #u Ala Ala Lys Leu Ser 1395 - # 1400 - # 1405 - - GGC CTC GGA ATC AAC GCT GTG GCG TAT TAC CG - #G GGG CTC GAT GTG TCC 4272 Gly Leu Gly Ile Asn Ala Val Ala Tyr Tyr Ar - #g Gly Leu Asp Val Ser 1410 - # 1415 - # 1420 - - GTC ATA CCA ACT ATC GGA GAC GTC GTT GTC GT - #G GCA ACA GAC GCT CTG 4320 Val Ile Pro Thr Ile Gly Asp Val Val Val Va - #l Ala Thr Asp Ala Leu 1425 1430 - # 1435 - # 1440 - - ATG ACG GGC TAT ACG GGC GAC TTT GAC TCA GT - #G ATC GAC TGT AAC ACA 4368 Met Thr Gly Tyr Thr Gly Asp Phe Asp Ser Va - #l Ile Asp Cys Asn Thr 1445 - # 1450 - # 1455 - - TGT GTC ACC CAG ACA GTC GAC TTC AGC TTG GA - #T CCC ACC TTC ACC ATT 4416 Cys Val Thr Gln Thr Val Asp Phe Ser Leu As - #p Pro Thr Phe Thr Ile 1460 - # 1465 - # 1470 - - GAG ACG ACG ACC GTG CCT CAA GAC GCA GTG TC - #G CGC TCG CAG CGG CGG 4464 Glu Thr Thr Thr Val Pro Gln Asp Ala Val Se - #r Arg Ser Gln Arg Arg 1475 - # 1480 - # 1485 - - GGT AGG ACT GGC AGG GGT AGG AGA GGC ATC TA - #C AGG TTT GTG ACT CCG 4512 Gly Arg Thr Gly Arg Gly Arg Arg Gly Ile Ty - #r Arg Phe Val Thr Pro 1490 - # 1495 - # 1500 - - GGA GAA CGG CCC TCG GGC ATG TTC GAT TCC TC - #G GTC CTG TGT GAG TGC 4560 Gly Glu Arg Pro Ser Gly Met Phe Asp Ser Se - #r Val Leu Cys Glu Cys 1505 1510 - # 1515 - # 1520 - - TAT GAC GCG GGC TGT GCT TGG TAC GAG CTC AC - #C CCG GCC GAG ACC TCG 4608 Tyr Asp Ala Gly Cys Ala Trp Tyr Glu Leu Th - #r Pro Ala Glu Thr Ser 1525 - # 1530 - # 1535 - - GTT AGG TTG CGG GCC TAC CTG AAC ACA CCA GG - #G TTG CCC GTT TGC CAG 4656 Val Arg Leu Arg Ala Tyr Leu Asn Thr Pro Gl - #y Leu Pro Val Cys Gln 1540 - # 1545 - # 1550 - - GAC CAC CTG GAG TTC TGG GAG AGT GTC TTC AC - #A GGC CTC ACC CAT ATA 4704 Asp His Leu Glu Phe Trp Glu Ser Val Phe Th - #r Gly Leu Thr His Ile 1555 - # 1560 - # 1565 - - GAT GCA CAC TTC TTG TCC CAG ACC AAG CAG GC - #A GGA GAC AAC TTC CCC 4752 Asp Ala His Phe Leu Ser Gln Thr Lys Gln Al - #a Gly Asp Asn Phe Pro 1570 - # 1575 - # 1580 - - TAC CTG GTA GCA TAC CAA GCC ACG GTG TGC GC - #C AGG GCT CAG GCC CCA 4800 Tyr Leu Val Ala Tyr Gln Ala Thr Val Cys Al - #a Arg Ala Gln Ala Pro 1585 1590 - # 1595 - # 1600 - - CCT CCA TCA TGG GAT CAA ATG TGG AAG TGT CT - #C ATA CGG CTG AAA CCT 4848 Pro Pro Ser Trp Asp Gln Met Trp Lys Cys Le - #u Ile Arg Leu Lys Pro 1605 - # 1610 - # 1615 - - ACG CTG CAC GGG CCA ACA CCC TTG CTG TAC AG - #G CTG GGA GCC GTC CAG 4896 Thr Leu His Gly Pro Thr Pro Leu Leu Tyr Ar - #g Leu Gly Ala Val Gln 1620 - # 1625 - # 1630 - - AAT GAG GTC ACC CTC ACC CAC CCC ATA ACC AA - #A TAC ATC ATG GCA TGC 4944 Asn Glu Val Thr Leu Thr His Pro Ile Thr Ly - #s Tyr Ile Met Ala Cys 1635 - # 1640 - # 1645 - - ATG TCG GCT GAC CTG GAG GTC GTC ACT AGC AC - #C TGG GTG CTG GTG GGC 4992 Met Ser Ala Asp Leu Glu Val Val Thr Ser Th - #r Trp Val Leu Val Gly 1650 - # 1655 - # 1660 - - GGA GTC CTT GCA GCT CTG GCC GCG TAT TGC CT - #G ACA ACA GGC AGT GTG 5040 Gly Val Leu Ala Ala Leu Ala Ala Tyr Cys Le - #u Thr Thr Gly Ser Val 1665 1670 - # 1675 - # 1680 - - GTC ATT GTG GGT AGG ATT ATC TTG TCC GGG AG - #G CCG GCC ATT GTT CCC 5088 Val Ile Val Gly Arg Ile Ile Leu Ser Gly Ar - #g Pro Ala Ile Val Pro 1685 - # 1690 - # 1695 - - GAC AGG GAG CTT CTC TAC CAG GAG TTC GAT GA - #A ATG GAA GAG TGC GCC 5136 Asp Arg Glu Leu Leu Tyr Gln Glu Phe Asp Gl - #u Met Glu Glu Cys Ala 1700 - # 1705 - # 1710 - - TCG CAC CTC CCT TAC ATC GAG CAG GGA ATG CA - #G CTC GCC GAG CAA TTC 5184 Ser His Leu Pro Tyr Ile Glu Gln Gly Met Gl - #n Leu Ala Glu Gln Phe 1715 - # 1720 - # 1725 - - AAG CAG AAA GCG CTC GGG TTA CTG CAA ACA GC - #C ACC AAA CAA GCG GAG 5232 Lys Gln Lys Ala Leu Gly Leu Leu Gln Thr Al - #a Thr Lys Gln Ala Glu 1730 - # 1735 - # 1740 - - GCT GCT GCT CCC GTG GTG GAG TCC AAG TGG CG - #A GCC CTT GAG ACA TTC 5280 Ala Ala Ala Pro Val Val Glu Ser Lys Trp Ar - #g Ala Leu Glu Thr Phe 1745 1750 - # 1755 - # 1760 - - TGG GCG AAG CAC ATG TGG AAT TTC ATC AGC GG - #G ATA CAG TAC TTA GCA 5328 Trp Ala Lys His Met Trp Asn Phe Ile Ser Gl - #y Ile Gln Tyr Leu Ala 1765 - # 1770 - # 1775 - - GGC TTA TCC ACT CTG CCT GGG AAC CCC GCA AT - #A GCA TCA TTG ATG GCA 5376 Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Il - #e Ala Ser Leu Met Ala 1780 - # 1785 - # 1790 - - TTC ACA GCC TCT ATC ACC AGC CCG CTC ACC AC - #C CAA AGT ACC CTC CTG 5424 Phe Thr Ala Ser Ile Thr Ser Pro Leu Thr Th - #r Gln Ser Thr Leu Leu 1795 - # 1800 - # 1805 - - TTT AAC ATC TTG GGG GGG TGG GTG GCT GCC CA - #A CTC GCC CCC CCC AGC 5472 Phe Asn Ile Leu Gly Gly Trp Val Ala Ala Gl - #n Leu Ala Pro Pro Ser 1810 - # 1815 - # 1820 - - GCC GCT TCG GCT TTC GTG GGC GCC GGC ATC GC - #C GGT GCG GCT GTT GGC 5520 Ala Ala Ser Ala Phe Val Gly Ala Gly Ile Al - #a Gly Ala Ala Val Gly 1825 1830 - # 1835 - # 1840 - - AGC ATA GGC CTT GGG AAG GTG CTT GTG GAC AT - #T CTG GCG GGT TAT GGA 5568 Ser Ile Gly Leu Gly Lys Val Leu Val Asp Il - #e Leu Ala Gly Tyr Gly 1845 - # 1850 - # 1855 - - GCA GGA GTG GCC GGC GCG CTC GTG GCC TTT AA - #G GTC ATG AGC GGC GAG 5616 Ala Gly Val Ala Gly Ala Leu Val Ala Phe Ly - #s Val Met Ser Gly Glu 1860 - # 1865 - # 1870 - - ATG CCC TCC ACC GAG GAC CTG GTC AAT CTA CT - #T CCT GCC ATC CTC TCT 5664 Met Pro Ser Thr Glu Asp Leu Val Asn Leu Le - #u Pro Ala Ile Leu Ser 1875 - # 1880 - # 1885 - - CCT GGC GCC CTG GTC GTC GGG GTC GTG TGT GC - #A GCA ATA CTG CGT CGA 5712 Pro Gly Ala Leu Val Val Gly Val Val Cys Al - #a Ala Ile Leu Arg Arg 1890 - # 1895 - # 1900 - - CAC GTG GGT CCG GGA GAG GGG GCT GTG CAG TG - #G ATG AAC CGG CTG ATA 5760 His Val Gly Pro Gly Glu Gly Ala Val Gln Tr - #p Met Asn Arg Leu Ile 1905 1910 - # 1915 - # 1920 - - GCG TTC GCC TCG CGG GGT AAT CAT GTT TCC CC - #C ACG CAC TAT GTG CCT 5808 Ala Phe Ala Ser Arg Gly Asn His Val Ser Pr - #o Thr His Tyr Val Pro 1925 - # 1930 - # 1935 - - GAG AGC GAC GCC GCA GCG CGT GTT ACT CAG AT - #C CTC TCC AGC CTT ACC 5856 Glu Ser Asp Ala Ala Ala Arg Val Thr Gln Il - #e Leu Ser Ser Leu Thr 1940 - # 1945 - # 1950 - - ATC ACT CAG CTG CTG AAA AGG CTC CAC CAG TG - #G ATT AAT GAA GAC TGC 5904 Ile Thr Gln Leu Leu Lys Arg Leu His Gln Tr - #p Ile Asn Glu Asp Cys 1955 - # 1960 - # 1965 - - TCC ACA CCG TGT TCC GGC TCG TGG CTA AGG GA - #T GTT TGG GAC TGG ATA 5952 Ser Thr Pro Cys Ser Gly Ser Trp Leu Arg As - #p Val Trp Asp Trp Ile 1970 - # 1975 - # 1980 - - TGC ACG GTG TTG ACT GAC TTC AAG ACC TGG CT - #C CAG TCC AAG CTC CTG 6000 Cys Thr Val Leu Thr Asp Phe Lys Thr Trp Le - #u Gln Ser Lys Leu Leu 1985 1990 - # 1995 - # 2000 - - CCG CAG CTA CCT GGA GTC CCT TTT TTC TCG TG - #C CAA CGC - # 6039 Pro Gln Leu Pro Gly Val Pro Phe Phe Ser Cy - #s Gln Arg 2005 - # 2010 - - - - (2) INFORMATION FOR SEQ ID NO:12: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2013 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: - - Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Th - #r Lys Arg Asn Thr Asn 1 5 - # 10 - # 15 - - Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gl - #y Gly Gln Ile Val Gly 20 - # 25 - # 30 - - Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Ar - #g Leu Gly Val Arg Ala 35 - # 40 - # 45 - - Pro Arg Lys Thr Ser Glu Arg Ser Gln Pro Ar - #g Gly Arg Arg Gln Pro 50 - # 55 - # 60 - - Ile Pro Lys Ala Arg Arg Pro Glu Gly Arg Th - #r Trp Ala Gln Pro Gly 65 - # 70 - # 75 - # 80 - - Tyr Pro Trp Pro Leu Tyr Gly Asn Glu Gly Le - #u Gly Trp Ala Gly Trp 85 - # 90 - # 95 - - Leu Leu Ser Pro Arg Gly Ser Arg Pro Ser Tr - #p Gly Pro Thr Asp Pro 100 - # 105 - # 110 - - Arg Arg Arg Ser Arg Asn Leu Gly Lys Val Il - #e Asp Thr Leu Thr Cys 115 - # 120 - # 125 - - Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Le - #u Val Gly Ala Pro Leu 130 - # 135 - # 140 - - Gly Gly Ala Ala Arg Ala Leu Ala His Gly Va - #l Arg Val Leu Glu Asp 145 1 - #50 1 - #55 1 -#60 - - Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gl - #y Cys Ser Phe SerIle 165 - # 170 - # 175 - - Phe Leu Leu Ala Leu Leu Ser Cys Leu Thr Th - #r Pro Ala Ser Ala Tyr 180 - # 185 - # 190 - - Glu Val His Asn Val Ser Gly Ile Tyr His Va - #l Thr Asn Asp Cys Ser 195 - # 200 - # 205 - - Asn Ala Ser Ile Val Tyr Glu Ala Ala Asp Le - #u Ile Met His Thr Pro 210 - # 215 - # 220 - - Gly Cys Val Pro Cys Val Arg Glu Gly Asn Se - #r Ser Arg Cys Trp Val 225 2 - #30 2 - #35 2 -#40 - - Ala Leu Thr Pro Thr Leu Ala Ala Arg Asn Va - #l Thr Ile Pro ThrThr 245 - # 250 - # 255 - - Thr Ile Arg Arg His Val Asp Leu Leu Val Gl - #y Ala Ala Ala Phe Cys 260 - # 265 - # 270 - - Ser Ala Met Tyr Val Gly Asp Leu Cys Gly Se - #r Val Phe Leu Val Ser 275 - # 280 - # 285 - - Gln Leu Phe Thr Phe Ser Pro Arg Arg His Va - #l Thr Leu Gln Asp Cys 290 - # 295 - # 300 - - Asn Cys Ser Ile Tyr Pro Gly His Val Ser Gl - #y His Arg Met Ala Trp 305 3 - #10 3 - #15 3 -#20 - - Asp Met Met Met Asn Trp Ser Pro Thr Thr Al - #a Leu Val Val SerGln 325 - # 330 - # 335 - - Leu Leu Arg Ile Pro Gln Ala Val Val Asp Me - #t Val Ala Gly Ala His 340 - # 345 - # 350 - - Trp Gly Val Leu Ala Gly Leu Ala Tyr Tyr Se - #r Met Ala Gly Asn Trp 355 - # 360 - # 365 - - Ala Lys Val Leu Ile Val Met Leu Leu Phe Al - #a Gly Val Asp Gly Asp 370 - # 375 - # 380 - - Thr His Val Thr Gly Gly Ala Gln Ala Lys Th - #r Thr Asn Arg Leu Val 385 3 - #90 3 - #95 4 -#00 - - Ser Met Phe Ala Ser Gly Pro Ser Gln Lys Il - #e Gln Leu Ile AsnThr 405 - # 410 - # 415 - - Asn Gly Ser Trp His Ile Asn Arg Thr Ala Le - #u Asn Cys Asn Asp Ser 420 - # 425 - # 430 - - Leu Gln Thr Gly Phe Leu Ala Ala Leu Phe Ty - #r Thr His Ser Phe Asn 435 - # 440 - # 445 - - Ser Ser Gly Cys Pro Glu Arg Met Ala Gln Cy - #s Arg Thr Ile Asp Lys 450 - # 455 - # 460 - - Phe Asp Gln Gly Trp Gly Pro Ile Thr Tyr Al - #a Glu Ser Ser Arg Ser 465 4 - #70 4 - #75 4 -#80 - - Asp Gln Arg Pro Tyr Cys Trp His Tyr Pro Pr - #o Pro Gln Cys ThrIle 485 - # 490 - # 495 - - Val Pro Ala Ser Glu Val Cys Gly Pro Val Ty - #r Cys Phe Thr Pro Ser 500 - # 505 - # 510 - - Pro Val Val Val Gly Thr Thr Asp Arg Phe Gl - #y Val Pro Thr Tyr Arg 515 - # 520 - # 525 - - Trp Gly Glu Asn Glu Thr Asp Val Leu Leu Le - #u Asn Asn Thr Arg Pro 530 - # 535 - # 540 - - Pro Gln Gly Asn Trp Phe Gly Cys Thr Trp Me - #t Asn Ser Thr Gly Phe 545 5 - #50 5 - #55 5 -#60 - - Thr Lys Thr Cys Gly Gly Pro Pro Cys Asn Il - #e Gly Gly Val GlyAsn 565 - # 570 - # 575 - - Asn Thr Leu Thr Cys Pro Thr Asp Cys Phe Ar - #g Lys His Pro Glu Ala 580 - # 585 - # 590 - - Thr Tyr Thr Lys Cys Gly Ser Gly Pro Trp Le - #u Thr Pro Arg Cys Met 595 - # 600 - # 605 - - Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pr - #o Cys Thr Val Asn Phe 610 - # 615 - # 620 - - Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gl - #y Val Glu His Arg Leu 625 6 - #30 6 - #35 6 -#40 - - Asn Ala Ala Cys Asn Trp Thr Arg Gly Glu Ar - #g Cys Asp Leu GluAsp 645 - # 650 - # 655 - - Arg Asp Arg Pro Glu Leu Ser Pro Leu Leu Le - #u Ser Thr Thr Glu Trp 660 - # 665 - # 670 - - Gln Val Leu Pro Cys Ser Phe Thr Thr Leu Pr - #o Ala Leu Ser Thr Gly 675 - # 680 - # 685 - - Leu Ile His Leu His Gln Asn Ile Val Asp Va - #l Gln Tyr Leu Tyr Gly 690 - # 695 - # 700 - - Ile Gly Ser Ala Val Val Ser Phe Ala Ile Ly - #s Trp Glu Tyr Val Leu 705 7 - #10 7 - #15 7 -#20 - - Leu Leu Phe Leu Leu Leu Ala Asp Ala Arg Va - #l Cys Ala Cys LeuTrp 725 - # 730 - # 735 - - Met Met Leu Leu Ile Ala Gln Ala Glu Ala Al - #a Leu Glu Asn Leu Val 740 - # 745 - # 750 - - Val Leu Asn Ser Ala Ser Val Ala Gly Ala Hi - #s Gly Ile Leu Ser Phe 755 - # 760 - # 765 - - Leu Val Phe Phe Cys Ala Ala Trp Tyr Ile Ly - #s Gly Arg Leu Val Pro 770 - # 775 - # 780 - - Gly Ala Thr Tyr Ala Leu Tyr Gly Val Trp Pr - #o Leu Leu Leu Leu Leu 785 7 - #90 7 - #95 8 -#00 - - Leu Ala Leu Pro Pro Arg Ala Tyr Ala Met As - #p Arg Glu Met AlaAla 805 - # 810 - # 815 - - Ser Cys Gly Gly Ala Val Phe Val Gly Leu Va - #l Leu Leu Thr Leu Ser 820 - # 825 - # 830 - - Pro Tyr Tyr Lys Val Phe Leu Ala Arg Leu Il - #e Trp Trp Leu Gln Tyr 835 - # 840 - # 845 - - Phe Thr Thr Arg Ala Glu Ala Asp Leu His Va - #l Trp Ile Pro Pro Leu 850 - # 855 - # 860 - - Asn Ala Arg Gly Gly Arg Asp Ala Ile Ile Le - #u Leu Met Cys Ala Val 865 8 - #70 8 - #75 8 -#80 - - His Pro Glu Leu Ile Phe Asp Ile Thr Lys Le - #u Leu Ile Ala IleLeu 885 - # 890 - # 895 - - Gly Pro Leu Met Val Leu Gln Ala Gly Ile Th - #r Arg Val Pro Tyr Phe 900 - # 905 - # 910 - - Val Arg Ala Gln Gly Leu Ile His Ala Cys Me - #t Leu Val Arg Lys Val 915 - # 920 - # 925 - - Ala Gly Gly His Tyr Val Gln Met Ala Phe Me - #t Lys Leu Gly Ala Leu 930 - # 935 - # 940 - - Thr Gly Thr Tyr Ile Tyr Asn His Leu Thr Pr - #o Leu Arg Asp Trp Pro 945 9 - #50 9 - #55 9 -#60 - - Arg Ala Gly Leu Arg Asp Leu Ala Val Ala Va - #l Glu Pro Val ValPhe 965 - # 970 - # 975 - - Ser Asp Met Glu Thr Lys Ile Ile Thr Trp Gl - #y Ala Asp Thr Ala Ala 980 - # 985 - # 990 - - Cys Gly Asp Ile Ile Leu Gly Leu Pro Val Se - #r Ala Arg Arg Gly Lys 995 - # 1000 - # 1005 - - Glu Ile Leu Leu Gly Pro Ala Asp Ser Leu Gl - #u Gly Arg Gly Leu Arg 1010 - # 1015 - # 1020 - - Leu Leu Ala Pro Ile Thr Ala Tyr Ser Gln Gl - #n Thr Arg Gly Leu Leu 1025 1030 - # 1035 - # 1040 - - Gly Cys Ile Ile Thr Ser Leu Thr Gly Arg As - #p Lys Asn Gln Val Glu 1045 - # 1050 - # 1055 - - Gly Glu Val Gln Val Val Ser Thr Ala Thr Gl - #n Ser Phe Leu Ala Thr 1060 - # 1065 - # 1070 - - Cys Val Asn Gly Val Cys Trp Thr Val Tyr Hi - #s Gly Ala Gly Ser Lys 1075 - # 1080 - # 1085 - - Thr Leu Ala Ala Pro Lys Gly Pro Ile Thr Gl - #n Met Tyr Thr Asn Val 1090 - # 1095 - # 1100 - - Asp Gln Asp Leu Val Gly Trp Pro Lys Pro Pr - #o Gly Ala Arg Ser Leu 1105 1110 - # 1115 - # 1120 - - Thr Pro Cys Thr Cys Gly Ser Ser Asp Leu Ty - #r Leu Val Thr Arg His 1125 - # 1130 - # 1135 - - Ala Asp Val Ile Pro Val Arg Arg Arg Gly As - #p Ser Arg Gly Ser Leu 1140 - # 1145 - # 1150 - - Leu Ser Pro Arg Pro Val Ser Tyr Leu Lys Gl - #y Ser Ser Gly Gly Pro 1155 - # 1160 - # 1165 - - Leu Leu Cys Pro Phe Gly His Ala Val Gly Il - #e Phe Arg Ala Ala Val 1170 - # 1175 - # 1180 - - Cys Thr Arg Gly Val Ala Lys Ala Val Asp Ph - #e Val Pro Val Glu Ser 1185 1190 - # 1195 - # 1200 - - Met Glu Thr Thr Met Arg Ser Pro Val Phe Th - #r Asp Asn Ser Ser Pro 1205 - # 1210 - # 1215 - - Pro Ala Val Pro Gln Ser Phe Gln Val Ala Hi - #s Leu His Ala Pro Thr 1220 - # 1225 - # 1230 - - Gly Ser Gly Lys Ser Thr Lys Val Pro Ala Al - #a Tyr Ala Ala Gln Gly 1235 - # 1240 - # 1245 - - Tyr Lys Val Leu Val Leu Asn Pro Ser Val Al - #a Ala Thr Leu Gly Phe 1250 - # 1255 - # 1260 - - Gly Ala Tyr Met Ser Lys Ala His Gly Ile As - #p Pro Asn Ile Arg Thr 1265 1270 - # 1275 - # 1280 - - Gly Val Arg Thr Ile Thr Thr Gly Ala Pro Va - #l Thr Tyr Ser Thr Tyr 1285 - # 1290 - # 1295 - - Gly Lys Phe Leu Ala Asp Gly Gly Cys Ser Gl - #y Gly Ala Tyr Asp Ile 1300 - # 1305 - # 1310 - - Ile Ile Cys Asp Glu Cys His Ser Thr Asp Se - #r Thr Thr Ile Leu Gly 1315 - # 1320 - # 1325 - - Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Al - #a Gly Ala Arg Leu Val 1330 - # 1335 - # 1340 - - Val Leu Ala Thr Ala Thr Pro Pro Gly Ser Va - #l Thr Val Pro His Pro 1345 1350 - # 1355 - # 1360 - - Asn Ile Glu Glu Val Ala Leu Ser Asn Thr Gl - #y Glu Ile Pro Phe Tyr 1365 - # 1370 - # 1375 - - Gly Lys Ala Ile Pro Ile Glu Ala Ile Arg Gl - #y Gly Arg His Leu Ile 1380 - # 1385 - # 1390 - - Phe Cys His Ser Lys Lys Lys Cys Asp Glu Le - #u Ala Ala Lys Leu Ser 1395 - # 1400 - # 1405 - - Gly Leu Gly Ile Asn Ala Val Ala Tyr Tyr Ar - #g Gly Leu Asp Val Ser 1410 - # 1415 - # 1420 - - Val Ile Pro Thr Ile Gly Asp Val Val Val Va - #l Ala Thr Asp Ala Leu 1425 1430 - # 1435 - # 1440 - - Met Thr Gly Tyr Thr Gly Asp Phe Asp Ser Va - #l Ile Asp Cys Asn Thr 1445 - # 1450 - # 1455 - - Cys Val Thr Gln Thr Val Asp Phe Ser Leu As - #p Pro Thr Phe Thr Ile 1460 - # 1465 - # 1470 - - Glu Thr Thr Thr Val Pro Gln Asp Ala Val Se - #r Arg Ser Gln Arg Arg 1475 - # 1480 - # 1485 - - Gly Arg Thr Gly Arg Gly Arg Arg Gly Ile Ty - #r Arg Phe Val Thr Pro 1490 - # 1495 - # 1500 - - Gly Glu Arg Pro Ser Gly Met Phe Asp Ser Se - #r Val Leu Cys Glu Cys 1505 1510 - # 1515 - # 1520 - - Tyr Asp Ala Gly Cys Ala Trp Tyr Glu Leu Th - #r Pro Ala Glu Thr Ser 1525 - # 1530 - # 1535 - - Val Arg Leu Arg Ala Tyr Leu Asn Thr Pro Gl - #y Leu Pro Val Cys Gln 1540 - # 1545 - # 1550 - - Asp His Leu Glu Phe Trp Glu Ser Val Phe Th - #r Gly Leu Thr His Ile 1555 - # 1560 - # 1565 - - Asp Ala His Phe Leu Ser Gln Thr Lys Gln Al - #a Gly Asp Asn Phe Pro 1570 - # 1575 - # 1580 - - Tyr Leu Val Ala Tyr Gln Ala Thr Val Cys Al - #a Arg Ala Gln Ala Pro 1585 1590 - # 1595 - # 1600 - - Pro Pro Ser Trp Asp Gln Met Trp Lys Cys Le - #u Ile Arg Leu Lys Pro 1605 - # 1610 - # 1615 - - Thr Leu His Gly Pro Thr Pro Leu Leu Tyr Ar - #g Leu Gly Ala Val Gln 1620 - # 1625 - # 1630 - - Asn Glu Val Thr Leu Thr His Pro Ile Thr Ly - #s Tyr Ile Met Ala Cys 1635 - # 1640 - # 1645 - - Met Ser Ala Asp Leu Glu Val Val Thr Ser Th - #r Trp Val Leu Val Gly 1650 - # 1655 - # 1660 - - Gly Val Leu Ala Ala Leu Ala Ala Tyr Cys Le - #u Thr Thr Gly Ser Val 1665 1670 - # 1675 - # 1680 - - Val Ile Val Gly Arg Ile Ile Leu Ser Gly Ar - #g Pro Ala Ile Val Pro 1685 - # 1690 - # 1695 - - Asp Arg Glu Leu Leu Tyr Gln Glu Phe Asp Gl - #u Met Glu Glu Cys Ala 1700 - # 1705 - # 1710 - - Ser His Leu Pro Tyr Ile Glu Gln Gly Met Gl - #n Leu Ala Glu Gln Phe 1715 - # 1720 - # 1725 - - Lys Gln Lys Ala Leu Gly Leu Leu Gln Thr Al - #a Thr Lys Gln Ala Glu 1730 - # 1735 - # 1740 - - Ala Ala Ala Pro Val Val Glu Ser Lys Trp Ar - #g Ala Leu Glu Thr Phe 1745 1750 - # 1755 - # 1760 - - Trp Ala Lys His Met Trp Asn Phe Ile Ser Gl - #y Ile Gln Tyr Leu Ala 1765 - # 1770 - # 1775 - - Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Il - #e Ala Ser Leu Met Ala 1780 - # 1785 - # 1790 - - Phe Thr Ala Ser Ile Thr Ser Pro Leu Thr Th - #r Gln Ser Thr Leu Leu 1795 - # 1800 - # 1805 - - Phe Asn Ile Leu Gly Gly Trp Val Ala Ala Gl - #n Leu Ala Pro Pro Ser 1810 - # 1815 - # 1820 - - Ala Ala Ser Ala Phe Val Gly Ala Gly Ile Al - #a Gly Ala Ala Val Gly 1825 1830 - # 1835 - # 1840 - - Ser Ile Gly Leu Gly Lys Val Leu Val Asp Il - #e Leu Ala Gly Tyr Gly 1845 - # 1850 - # 1855 - - Ala Gly Val Ala Gly Ala Leu Val Ala Phe Ly - #s Val Met Ser Gly Glu 1860 - # 1865 - # 1870 - - Met Pro Ser Thr Glu Asp Leu Val Asn Leu Le - #u Pro Ala Ile Leu Ser 1875 - # 1880 - # 1885 - - Pro Gly Ala Leu Val Val Gly Val Val Cys Al - #a Ala Ile Leu Arg Arg 1890 - # 1895 - # 1900 - - His Val Gly Pro Gly Glu Gly Ala Val Gln Tr - #p Met Asn Arg Leu Ile 1905 1910 - # 1915 - # 1920 - - Ala Phe Ala Ser Arg Gly Asn His Val Ser Pr - #o Thr His Tyr Val Pro 1925 - # 1930 - # 1935 - - Glu Ser Asp Ala Ala Ala Arg Val Thr Gln Il - #e Leu Ser Ser Leu Thr 1940 - # 1945 - # 1950 - - Ile Thr Gln Leu Leu Lys Arg Leu His Gln Tr - #p Ile Asn Glu Asp Cys 1955 - # 1960 - # 1965 - - Ser Thr Pro Cys Ser Gly Ser Trp Leu Arg As - #p Val Trp Asp Trp Ile 1970 - # 1975 - # 1980 - - Cys Thr Val Leu Thr Asp Phe Lys Thr Trp Le - #u Gln Ser Lys Leu Leu 1985 1990 - # 1995 - # 2000 - - Pro Gln Leu Pro Gly Val Pro Phe Phe Ser Cy - #s Gln Arg 2005 - # 2010 - - - - (2) INFORMATION FOR SEQ ID NO:13: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9030 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..9030 (D) OTHER INFORMATION: - #/note: "sequence = 333 - 9362 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..9030 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13: - - ATG AGC ACG AAT CCT AAA CCT CAA AGA AAA AC - #C AAA CGT AAC ACC AAC 48 Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Th - #r Lys Arg Asn Thr Asn 1 5 - # 10 - # 15 - - CGC CGC CCA CAG GAC GTC AAG TTC CCG GGC GG - #T GGT CAG ATC GTT GGT 96 Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gl - #y Gly Gln Ile Val Gly 20 - # 25 - # 30 - - GGA GTT TAC CTG TTG CCG CGC AGG GGC CCC AG - #G TTG GGT GTG CGC GCG 144 Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Ar - #g Leu Gly Val Arg Ala 35 - # 40 - # 45 - - CCC AGG AAG ACT TCC GAG CGG TCG CAA CCT CG - #T GGA AGG CGA CAA CCT 192 Pro Arg Lys Thr Ser Glu Arg Ser Gln Pro Ar - #g Gly Arg Arg Gln Pro 50 - # 55 - # 60 - - ATC CCC AAG GCT CGC CGG CCC GAG GGC AGG AC - #C TGG GCT CAG CCC GGG 240 Ile Pro Lys Ala Arg Arg Pro Glu Gly Arg Th - #r Trp Ala Gln Pro Gly 65 - # 70 - # 75 - # 80 - - TAC CCT TGG CCT CTC TAT GGC AAT GAG GGC TT - #A GGG TGG GCA GGA TGG 288 Tyr Pro Trp Pro Leu Tyr Gly Asn Glu Gly Le - #u Gly Trp Ala Gly Trp 85 - # 90 - # 95 - - CTC CTG TCA CCC CGC GGC TCC CGG CCT AGT TG - #G GGC CCC ACG GAC CCC 336 Leu Leu Ser Pro Arg Gly Ser Arg Pro Ser Tr - #p Gly Pro Thr Asp Pro 100 - # 105 - # 110 - - CGG CGT AGG TCG CGT AAT TTG GGT AAG GTC AT - #C GAT ACC CTC ACA TGC 384 Arg Arg Arg Ser Arg Asn Leu Gly Lys Val Il - #e Asp Thr Leu Thr Cys 115 - # 120 - # 125 - - GGC TTC GCC GAT CTC ATG GGG TAC ATT CCG CT - #C GTC GGC GCC CCC CTG 432 Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Le - #u Val Gly Ala Pro Leu 130 - # 135 - # 140 - - GGG GGC GCT GCC AGG GCC CTG GCA CAT GGT GT - #C CGG GTT CTG GAG GAC 480 Gly Gly Ala Ala Arg Ala Leu Ala His Gly Va - #l Arg Val Leu Glu Asp 145 1 - #50 1 - #55 1 -#60 - - GGC GTG AAC TAT GCA ACA GGG AAT CTG CCC GG - #T TGC TCT TTT TCTATC 528 Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gl - #y Cys Ser Phe Ser Ile 165 - # 170 - # 175 - - TTC CTC TTG GCT CTG CTG TCC TGC CTG ACC AC - #C CCA GCT TCC GCT TAC 576 Phe Leu Leu Ala Leu Leu Ser Cys Leu Thr Th - #r Pro Ala Ser Ala Tyr 180 - # 185 - # 190 - - GAA GTG CAC AAC GTG TCC GGG ATA TAT CAT GT - #C ACG AAC GAC TGC TCC 624 Glu Val His Asn Val Ser Gly Ile Tyr His Va - #l Thr Asn Asp Cys Ser 195 - # 200 - # 205 - - AAC GCA AGC ATT GTG TAT GAG GCA GCG GAC TT - #G ATC ATG CAT ACT CCT 672 Asn Ala Ser Ile Val Tyr Glu Ala Ala Asp Le - #u Ile Met His Thr Pro 210 - # 215 - # 220 - - GGG TGC GTG CCC TGC GTT CGG GAA GGC AAC TC - #C TCC CGC TGC TGG GTA 720 Gly Cys Val Pro Cys Val Arg Glu Gly Asn Se - #r Ser Arg Cys Trp Val 225 2 - #30 2 - #35 2 -#40 - - GCG CTC ACT CCC ACG CTC GCA GCC AGG AAC GT - #C ACC ATC CCC ACCACG 768 Ala Leu Thr Pro Thr Leu Ala Ala Arg Asn Va - #l Thr Ile Pro Thr Thr 245 - # 250 - # 255 - - ACG ATA CGA CGC CAC GTC GAT CTG CTC GTT GG - #G GCG GCT GCT TTC TGT 816 Thr Ile Arg Arg His Val Asp Leu Leu Val Gl - #y Ala Ala Ala Phe Cys 260 - # 265 - # 270 - - TCC GCT ATG TAC GTG GGG GAC CTC TGC GGA TC - #T GTT TTC CTC GTC TCT 864 Ser Ala Met Tyr Val Gly Asp Leu Cys Gly Se - #r Val Phe Leu Val Ser 275 - # 280 - # 285 - - CAG CTG TTC ACC TTC TCG CCT CGC CGG CAT GT - #G ACA TTA CAG GAC TGT 912 Gln Leu Phe Thr Phe Ser Pro Arg Arg His Va - #l Thr Leu Gln Asp Cys 290 - # 295 - # 300 - - AAC TGC TCA ATT TAT CCC GGC CAT GTG TCG GG - #T CAC CGT ATG GCT TGG 960 Asn Cys Ser Ile Tyr Pro Gly His Val Ser Gl - #y His Arg Met Ala Trp 305 3 - #10 3 - #15 3 -#20 - - GAC ATG ATG ATG AAC TGG TCG CCC ACA ACA GC - #C CTA GTG GTG TCGCAG 1008 Asp Met Met Met Asn Trp Ser Pro Thr Thr Al - #a Leu Val Val Ser Gln 325 - # 330 - # 335 - - TTA CTC CGG ATC CCA CAA GCC GTC GTG GAC AT - #G GTG GCG GGG GCC CAC 1056 Leu Leu Arg Ile Pro Gln Ala Val Val Asp Me - #t Val Ala Gly Ala His 340 - # 345 - # 350 - - TGG GGA GTC CTG GCG GGC CTT GCC TAC TAT TC - #C ATG GCG GGG AAC TGG 1104 Trp Gly Val Leu Ala Gly Leu Ala Tyr Tyr Se - #r Met Ala Gly Asn Trp 355 - # 360 - # 365 - - GCT AAG GTT CTG ATT GTG ATG CTA CTT TTT GC - #T GGC GTT GAC GGG GAT 1152 Ala Lys Val Leu Ile Val Met Leu Leu Phe Al - #a Gly Val Asp Gly Asp 370 - # 375 - # 380 - - ACC CAC GTG ACA GGG GGG GCG CAA GCC AAA AC - #C ACC AAC AGG CTC GTG 1200 Thr His Val Thr Gly Gly Ala Gln Ala Lys Th - #r Thr Asn Arg Leu Val 385 3 - #90 3 - #95 4 -#00 - - TCC ATG TTC GCA AGT GGG CCG TCT CAG AAA AT - #C CAG CTT ATA AACACC 1248 Ser Met Phe Ala Ser Gly Pro Ser Gln Lys Il - #e Gln Leu Ile Asn Thr 405 - # 410 - # 415 - - AAT GGG AGT TGG CAC ATC AAC AGG ACT GCC CT - #G AAC TGC AAT GAC TCT 1296 Asn Gly Ser Trp His Ile Asn Arg Thr Ala Le - #u Asn Cys Asn Asp Ser 420 - # 425 - # 430 - - CTC CAG ACT GGG TTT CTT GCC GCG CTG TTC TA - #C ACA CAT AGT TTC AAC 1344 Leu Gln Thr Gly Phe Leu Ala Ala Leu Phe Ty - #r Thr His Ser Phe Asn 435 - # 440 - # 445 - - TCG TCC GGG TGC CCA GAG CGC ATG GCC CAG TG - #C CGC ACC ATT GAC AAG 1392 Ser Ser Gly Cys Pro Glu Arg Met Ala Gln Cy - #s Arg Thr Ile Asp Lys 450 - # 455 - # 460 - - TTC GAC CAG GGA TGG GGT CCC ATT ACT TAT GC - #T GAG TCT AGC AGA TCA 1440 Phe Asp Gln Gly Trp Gly Pro Ile Thr Tyr Al - #a Glu Ser Ser Arg Ser 465 4 - #70 4 - #75 4 -#80 - - GAC CAG AGG CCA TAT TGC TGG CAC TAC CCA CC - #T CCA CAA TGT ACCATC 1488 Asp Gln Arg Pro Tyr Cys Trp His Tyr Pro Pr - #o Pro Gln Cys Thr Ile 485 - # 490 - # 495 - - GTA CCT GCG TCG GAG GTG TGC GGC CCA GTG TA - #C TGC TTC ACC CCA AGC 1536 Val Pro Ala Ser Glu Val Cys Gly Pro Val Ty - #r Cys Phe Thr Pro Ser 500 - # 505 - # 510 - - CCT GTC GTC GTG GGG ACG ACC GAT CGT TTC GG - #T GTC CCT ACG TAT AGA 1584 Pro Val Val Val Gly Thr Thr Asp Arg Phe Gl - #y Val Pro Thr Tyr Arg 515 - # 520 - # 525 - - TGG GGG GAG AAC GAG ACT GAC GTG CTG CTG CT - #C AAC AAC ACG CGG CCG 1632 Trp Gly Glu Asn Glu Thr Asp Val Leu Leu Le - #u Asn Asn Thr Arg Pro 530 - # 535 - # 540 - - CCG CAA GGC AAC TGG TTC GGC TGC ACA TGG AT - #G AAT AGC ACC GGG TTC 1680 Pro Gln Gly Asn Trp Phe Gly Cys Thr Trp Me - #t Asn Ser Thr Gly Phe 545 5 - #50 5 - #55 5 -#60 - - ACC AAG ACA TGT GGG GGG CCC CCG TGT AAC AT - #C GGG GGG GTC GGCAAC 1728 Thr Lys Thr Cys Gly Gly Pro Pro Cys Asn Il - #e Gly Gly Val Gly Asn 565 - # 570 - # 575 - - AAC ACC CTG ACC TGC CCC ACG GAC TGC TTC CG - #G AAG CAC CCC GAG GCT 1776 Asn Thr Leu Thr Cys Pro Thr Asp Cys Phe Ar - #g Lys His Pro Glu Ala 580 - # 585 - # 590 - - ACC TAC ACA AAA TGT GGT TCG GGG CCT TGG CT - #G ACA CCT AGG TGC ATG 1824 Thr Tyr Thr Lys Cys Gly Ser Gly Pro Trp Le - #u Thr Pro Arg Cys Met 595 - # 600 - # 605 - - GTT GAC TAT CCA TAC AGG CTC TGG CAT TAC CC - #C TGC ACT GTT AAC TTT 1872 Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pr - #o Cys Thr Val Asn Phe 610 - # 615 - # 620 - - ACC ATC TTC AAG GTT AGG ATG TAT GTG GGG GG - #G GTG GAG CAC AGG CTC 1920 Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gl - #y Val Glu His Arg Leu 625 6 - #30 6 - #35 6 -#40 - - AAT GCT GCA TGC AAT TGG ACC CGA GGA GAG CG - #T TGT GAC TTG GAGGAC 1968 Asn Ala Ala Cys Asn Trp Thr Arg Gly Glu Ar - #g Cys Asp Leu Glu Asp 645 - # 650 - # 655 - - AGG GAT AGG CCG GAG CTC AGC CCG CTG CTG CT - #G TCT ACA ACA GAG TGG 2016 Arg Asp Arg Pro Glu Leu Ser Pro Leu Leu Le - #u Ser Thr Thr Glu Trp 660 - # 665 - # 670 - - CAG GTA CTG CCC TGT TCC TTC ACC ACC CTA CC - #A GCT CTG TCC ACT GGC 2064 Gln Val Leu Pro Cys Ser Phe Thr Thr Leu Pr - #o Ala Leu Ser Thr Gly 675 - # 680 - # 685 - - TTG ATT CAC CTC CAT CAG AAC ATC GTG GAC GT - #G CAA TAC CTA TAC GGT 2112 Leu Ile His Leu His Gln Asn Ile Val Asp Va - #l Gln Tyr Leu Tyr Gly 690 - # 695 - # 700 - - ATA GGG TCA GCG GTT GTC TCC TTT GCA ATC AA - #A TGG GAG TAT GTC CTG 2160 Ile Gly Ser Ala Val Val Ser Phe Ala Ile Ly - #s Trp Glu Tyr Val Leu 705 7 - #10 7 - #15 7 -#20 - - TTG CTT TTC CTT CTC CTA GCG GAC GCA CGT GT - #C TGT GCC TGC TTGTGG 2208 Leu Leu Phe Leu Leu Leu Ala Asp Ala Arg Va - #l Cys Ala Cys Leu Trp 725 - # 730 - # 735 - - ATG ATG CTG CTG ATA GCC CAG GCC GAG GCC GC - #C TTG GAG AAC CTG GTG 2256 Met Met Leu Leu Ile Ala Gln Ala Glu Ala Al - #a Leu Glu Asn Leu Val 740 - # 745 - # 750 - - GTC CTC AAT TCG GCG TCT GTG GCC GGC GCA CA - #T GGC ATC CTC TCC TTC 2304 Val Leu Asn Ser Ala Ser Val Ala Gly Ala Hi - #s Gly Ile Leu Ser Phe 755 - # 760 - # 765 - - CTT GTG TTC TTC TGT GCC GCC TGG TAC ATC AA - #A GGC AGG CTG GTC CCT 2352 Leu Val Phe Phe Cys Ala Ala Trp Tyr Ile Ly - #s Gly Arg Leu Val Pro 770 - # 775 - # 780 - - GGG GCG ACA TAT GCT CTT TAT GGC GTG TGG CC - #G CTG CTC CTG CTC TTG 2400 Gly Ala Thr Tyr Ala Leu Tyr Gly Val Trp Pr - #o Leu Leu Leu Leu Leu 785 7 - #90 7 - #95 8 -#00 - - CTG GCA TTA CCA CCG CGA GCT TAC GCC ATG GA - #C CGG GAG ATG GCTGCA 2448 Leu Ala Leu Pro Pro Arg Ala Tyr Ala Met As - #p Arg Glu Met Ala Ala 805 - # 810 - # 815 - - TCG TGC GGA GGC GCG GTT TTT GTG GGT CTG GT - #A CTC CTG ACT TTG TCA 2496 Ser Cys Gly Gly Ala Val Phe Val Gly Leu Va - #l Leu Leu Thr Leu Ser 820 - # 825 - # 830 - - CCA TAC TAC AAG GTG TTC CTC GCT AGG CTC AT - #A TGG TGG TTA CAA TAT 2544 Pro Tyr Tyr Lys Val Phe Leu Ala Arg Leu Il - #e Trp Trp Leu Gln Tyr 835 - # 840 - # 845 - - TTT ACC ACC AGA GCC GAG GCG GAC TTA CAT GT - #G TGG ATC CCC CCC CTC 2592 Phe Thr Thr Arg Ala Glu Ala Asp Leu His Va - #l Trp Ile Pro Pro Leu 850 - # 855 - # 860 - - AAC GCT CGG GGA GGC CGC GAT GCC ATC ATC CT - #C CTC ATG TGC GCA GTC 2640 Asn Ala Arg Gly Gly Arg Asp Ala Ile Ile Le - #u Leu Met Cys Ala Val 865 8 - #70 8 - #75 8 -#80 - - CAT CCA GAG CTA ATC TTT GAC ATC ACC AAA CT - #T CTA ATT GCC ATACTC 2688 His Pro Glu Leu Ile Phe Asp Ile Thr Lys Le - #u Leu Ile Ala Ile Leu 885 - # 890 - # 895 - - GGT CCG CTC ATG GTG CTC CAA GCT GGC ATA AC - #C AGA GTG CCG TAC TTC 2736 Gly Pro Leu Met Val Leu Gln Ala Gly Ile Th - #r Arg Val Pro Tyr Phe 900 - # 905 - # 910 - - GTG CGC GCT CAA GGG CTC ATT CAT GCA TGC AT - #G TTA GTG CGG AAG GTC 2784 Val Arg Ala Gln Gly Leu Ile His Ala Cys Me - #t Leu Val Arg Lys Val 915 - # 920 - # 925 - - GCT GGG GGT CAT TAT GTC CAA ATG GCC TTC AT - #G AAG CTG GGC GCG CTG 2832 Ala Gly Gly His Tyr Val Gln Met Ala Phe Me - #t Lys Leu Gly Ala Leu 930 - # 935 - # 940 - - ACA GGC ACG TAC ATT TAC AAC CAT CTT ACC CC - #G CTA CGG GAT TGG CCA 2880 Thr Gly Thr Tyr Ile Tyr Asn His Leu Thr Pr - #o Leu Arg Asp Trp Pro 945 9 - #50 9 - #55 9 -#60 - - CGC GCG GGC CTA CGA GAC CTT GCG GTG GCA GT - #G GAG CCC GTC GTCTTC 2928 Arg Ala Gly Leu Arg Asp Leu Ala Val Ala Va - #l Glu Pro Val Val Phe 965 - # 970 - # 975 - - TCC GAC ATG GAG ACC AAG ATC ATC ACC TGG GG - #A GCA GAC ACC GCG GCG 2976 Ser Asp Met Glu Thr Lys Ile Ile Thr Trp Gl - #y Ala Asp Thr Ala Ala 980 - # 985 - # 990 - - TGT GGG GAC ATC ATC TTG GGT CTG CCC GTC TC - #C GCC CGA AGG GGA AAG 3024 Cys Gly Asp Ile Ile Leu Gly Leu Pro Val Se - #r Ala Arg Arg Gly Lys 995 - # 1000 - # 1005 - - GAG ATA CTC CTG GGC CCG GCC GAT AGT CTT GA - #A GGG CGG GGG TTG CGA 3072 Glu Ile Leu Leu Gly Pro Ala Asp Ser Leu Gl - #u Gly Arg Gly Leu Arg 1010 - # 1015 - # 1020 - - CTC CTC GCG CCC ATC ACG GCC TAC TCC CAA CA - #G ACG CGG GGC CTA CTT 3120 Leu Leu Ala Pro Ile Thr Ala Tyr Ser Gln Gl - #n Thr Arg Gly Leu Leu 1025 1030 - # 1035 - # 1040 - - GGT TGC ATC ATC ACT AGC CTT ACA GGC CGG GA - #C AAG AAC CAG GTC GAG 3168 Gly Cys Ile Ile Thr Ser Leu Thr Gly Arg As - #p Lys Asn Gln Val Glu 1045 - # 1050 - # 1055 - - GGA GAG GTT CAG GTG GTT TCC ACC GCA ACA CA - #A TCC TTC CTG GCG ACC 3216 Gly Glu Val Gln Val Val Ser Thr Ala Thr Gl - #n Ser Phe Leu Ala Thr 1060 - # 1065 - # 1070 - - TGC GTC AAC GGC GTG TGT TGG ACC GTT TAC CA - #T GGT GCT GGC TCA AAG 3264 Cys Val Asn Gly Val Cys Trp Thr Val Tyr Hi - #s Gly Ala Gly Ser Lys 1075 - # 1080 - # 1085 - - ACC TTA GCC GCG CCA AAG GGG CCA ATC ACC CA - #G ATG TAC ACT AAT GTG 3312 Thr Leu Ala Ala Pro Lys Gly Pro Ile Thr Gl - #n Met Tyr Thr Asn Val 1090 - # 1095 - # 1100 - - GAC CAG GAC CTC GTC GGC TGG CCC AAG CCC CC - #C GGG GCG CGT TCC TTG 3360 Asp Gln Asp Leu Val Gly Trp Pro Lys Pro Pr - #o Gly Ala Arg Ser Leu 1105 1110 - # 1115 - # 1120 - - ACA CCA TGC ACC TGT GGC AGC TCA GAC CTT TA - #C TTG GTC ACG AGA CAT 3408 Thr Pro Cys Thr Cys Gly Ser Ser Asp Leu Ty - #r Leu Val Thr Arg His 1125 - # 1130 - # 1135 - - GCT GAC GTC ATT CCG GTG CGC CGG CGG GGC GA - #C AGT AGG GGG AGC CTG 3456 Ala Asp Val Ile Pro Val Arg Arg Arg Gly As - #p Ser Arg Gly Ser Leu 1140 - # 1145 - # 1150 - - CTC TCC CCC AGG CCT GTC TCC TAC TTG AAG GG - #C TCT TCG GGT GGT CCA 3504 Leu Ser Pro Arg Pro Val Ser Tyr Leu Lys Gl - #y Ser Ser Gly Gly Pro 1155 - # 1160 - # 1165 - - CTG CTC TGC CCC TTC GGG CAC GCT GTG GGC AT - #C TTC CGG GCT GCC GTA 3552 Leu Leu Cys Pro Phe Gly His Ala Val Gly Il - #e Phe Arg Ala Ala Val 1170 - # 1175 - # 1180 - - TGC ACC CGG GGG GTT GCG AAG GCG GTG GAC TT - #T GTG CCC GTA GAG TCC 3600 Cys Thr Arg Gly Val Ala Lys Ala Val Asp Ph - #e Val Pro Val Glu Ser 1185 1190 - # 1195 - # 1200 - - ATG GAA ACT ACT ATG CGG TCT CCG GTC TTC AC - #G GAC AAC TCA TCC CCC 3648 Met Glu Thr Thr Met Arg Ser Pro Val Phe Th - #r Asp Asn Ser Ser Pro 1205 - # 1210 - # 1215 - - CCG GCC GTA CCG CAG TCA TTT CAA GTG GCC CA - #C CTA CAC GCT CCC ACT 3696 Pro Ala Val Pro Gln Ser Phe Gln Val Ala Hi - #s Leu His Ala Pro Thr 1220 - # 1225 - # 1230 - - GGC AGC GGC AAG AGT ACT AAA GTG CCG GCT GC - #A TAT GCA GCC CAA GGG 3744 Gly Ser Gly Lys Ser Thr Lys Val Pro Ala Al - #a Tyr Ala Ala Gln Gly 1235 - # 1240 - # 1245 - - TAC AAG GTG CTC GTC CTC AAT CCG TCC GTT GC - #C GCT ACC TTA GGG TTT 3792 Tyr Lys Val Leu Val Leu Asn Pro Ser Val Al - #a Ala Thr Leu Gly Phe 1250 - # 1255 - # 1260 - - GGG GCG TAT ATG TCT AAG GCA CAC GGT ATT GA - #C CCC AAC ATC AGA ACT 3840 Gly Ala Tyr Met Ser Lys Ala His Gly Ile As - #p Pro Asn Ile Arg Thr 1265 1270 - # 1275 - # 1280 - - GGG GTA AGG ACC ATT ACC ACA GGC GCC CCC GT - #C ACA TAC TCT ACC TAT 3888 Gly Val Arg Thr Ile Thr Thr Gly Ala Pro Va - #l Thr Tyr Ser Thr Tyr 1285 - # 1290 - # 1295 - - GGC AAG TTT CTT GCC GAT GGT GGT TGC TCT GG - #G GGC GCT TAT GAC ATC 3936 Gly Lys Phe Leu Ala Asp Gly Gly Cys Ser Gl - #y Gly Ala Tyr Asp Ile 1300 - # 1305 - # 1310 - - ATA ATA TGT GAT GAG TGC CAT TCA ACT GAC TC - #G ACT ACA ATC TTG GGC 3984 Ile Ile Cys Asp Glu Cys His Ser Thr Asp Se - #r Thr Thr Ile Leu Gly 1315 - # 1320 - # 1325 - - ATC GGC ACA GTC CTG GAC CAA GCG GAG ACG GC - #T GGA GCG CGG CTT GTC 4032 Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Al - #a Gly Ala Arg Leu Val 1330 - # 1335 - # 1340 - - GTG CTC GCC ACC GCT ACG CCT CCG GGA TCG GT - #C ACC GTG CCA CAC CCA 4080 Val Leu Ala Thr Ala Thr Pro Pro Gly Ser Va - #l Thr Val Pro His Pro 1345 1350 - # 1355 - # 1360 - - AAC ATC GAG GAG GTG GCC CTG TCT AAT ACT GG - #A GAG ATC CCC TTC TAT 4128 Asn Ile Glu Glu Val Ala Leu Ser Asn Thr Gl - #y Glu Ile Pro Phe Tyr 1365 - # 1370 - # 1375 - - GGC AAA GCC ATC CCC ATT GAA GCC ATC AGG GG - #G GGA AGG CAT CTC ATT 4176 Gly Lys Ala Ile Pro Ile Glu Ala Ile Arg Gl - #y Gly Arg His Leu Ile 1380 - # 1385 - # 1390 - - TTC TGT CAT TCC AAG AAG AAG TGC GAC GAG CT - #C GCC GCA AAG CTG TCA 4224 Phe Cys His Ser Lys Lys Lys Cys Asp Glu Le - #u Ala Ala Lys Leu Ser 1395 - # 1400 - # 1405 - - GGC CTC GGA ATC AAC GCT GTG GCG TAT TAC CG - #G GGG CTC GAT GTG TCC 4272 Gly Leu Gly Ile Asn Ala Val Ala Tyr Tyr Ar - #g Gly Leu Asp Val Ser 1410 - # 1415 - # 1420 - - GTC ATA CCA ACT ATC GGA GAC GTC GTT GTC GT - #G GCA ACA GAC GCT CTG 4320 Val Ile Pro Thr Ile Gly Asp Val Val Val Va - #l Ala Thr Asp Ala Leu 1425 1430 - # 1435 - # 1440 - - ATG ACG GGC TAT ACG GGC GAC TTT GAC TCA GT - #G ATC GAC TGT AAC ACA 4368 Met Thr Gly Tyr Thr Gly Asp Phe Asp Ser Va - #l Ile Asp Cys Asn Thr 1445 - # 1450 - # 1455 - - TGT GTC ACC CAG ACA GTC GAC TTC AGC TTG GA - #T CCC ACC TTC ACC ATT 4416 Cys Val Thr Gln Thr Val Asp Phe Ser Leu As - #p Pro Thr Phe Thr Ile 1460 - # 1465 - # 1470 - - GAG ACG ACG ACC GTG CCT CAA GAC GCA GTG TC - #G CGC TCG CAG CGG CGG 4464 Glu Thr Thr Thr Val Pro Gln Asp Ala Val Se - #r Arg Ser Gln Arg Arg 1475 - # 1480 - # 1485 - - GGT AGG ACT GGC AGG GGT AGG AGA GGC ATC TA - #C AGG TTT GTG ACT CCG 4512 Gly Arg Thr Gly Arg Gly Arg Arg Gly Ile Ty - #r Arg Phe Val Thr Pro 1490 - # 1495 - # 1500 - - GGA GAA CGG CCC TCG GGC ATG TTC GAT TCC TC - #G GTC CTG TGT GAG TGC 4560 Gly Glu Arg Pro Ser Gly Met Phe Asp Ser Se - #r Val Leu Cys Glu Cys 1505 1510 - # 1515 - # 1520 - - TAT GAC GCG GGC TGT GCT TGG TAC GAG CTC AC - #C CCG GCC GAG ACC TCG 4608 Tyr Asp Ala Gly Cys Ala Trp Tyr Glu Leu Th - #r Pro Ala Glu Thr Ser 1525 - # 1530 - # 1535 - - GTT AGG TTG CGG GCC TAC CTG AAC ACA CCA GG - #G TTG CCC GTT TGC CAG 4656 Val Arg Leu Arg Ala Tyr Leu Asn Thr Pro Gl - #y Leu Pro Val Cys Gln 1540 - # 1545 - # 1550 - - GAC CAC CTG GAG TTC TGG GAG AGT GTC TTC AC - #A GGC CTC ACC CAT ATA 4704 Asp His Leu Glu Phe Trp Glu Ser Val Phe Th - #r Gly Leu Thr His Ile 1555 - # 1560 - # 1565 - - GAT GCA CAC TTC TTG TCC CAG ACC AAG CAG GC - #A GGA GAC AAC TTC CCC 4752 Asp Ala His Phe Leu Ser Gln Thr Lys Gln Al - #a Gly Asp Asn Phe Pro 1570 - # 1575 - # 1580 - - TAC CTG GTA GCA TAC CAA GCC ACG GTG TGC GC - #C AGG GCT CAG GCC CCA 4800 Tyr Leu Val Ala Tyr Gln Ala Thr Val Cys Al - #a Arg Ala Gln Ala Pro 1585 1590 - # 1595 - # 1600 - - CCT CCA TCA TGG GAT CAA ATG TGG AAG TGT CT - #C ATA CGG CTG AAA CCT 4848 Pro Pro Ser Trp Asp Gln Met Trp Lys Cys Le - #u Ile Arg Leu Lys Pro 1605 - # 1610 - # 1615 - - ACG CTG CAC GGG CCA ACA CCC TTG CTG TAC AG - #G CTG GGA GCC GTC CAG 4896 Thr Leu His Gly Pro Thr Pro Leu Leu Tyr Ar - #g Leu Gly Ala Val Gln 1620 - # 1625 - # 1630 - - AAT GAG GTC ACC CTC ACC CAC CCC ATA ACC AA - #A TAC ATC ATG GCA TGC 4944 Asn Glu Val Thr Leu Thr His Pro Ile Thr Ly - #s Tyr Ile Met Ala Cys 1635 - # 1640 - # 1645 - - ATG TCG GCT GAC CTG GAG GTC GTC ACT AGC AC - #C TGG GTG CTG GTG GGC 4992 Met Ser Ala Asp Leu Glu Val Val Thr Ser Th - #r Trp Val Leu Val Gly 1650 - # 1655 - # 1660 - - GGA GTC CTT GCA GCT CTG GCC GCG TAT TGC CT - #G ACA ACA GGC AGT GTG 5040 Gly Val Leu Ala Ala Leu Ala Ala Tyr Cys Le - #u Thr Thr Gly Ser Val 1665 1670 - # 1675 - # 1680 - - GTC ATT GTG GGT AGG ATT ATC TTG TCC GGG AG - #G CCG GCC ATT GTT CCC 5088 Val Ile Val Gly Arg Ile Ile Leu Ser Gly Ar - #g Pro Ala Ile Val Pro 1685 - # 1690 - # 1695 - - GAC AGG GAG CTT CTC TAC CAG GAG TTC GAT GA - #A ATG GAA GAG TGC GCC 5136 Asp Arg Glu Leu Leu Tyr Gln Glu Phe Asp Gl - #u Met Glu Glu Cys Ala 1700 - # 1705 - # 1710 - - TCG CAC CTC CCT TAC ATC GAG CAG GGA ATG CA - #G CTC GCC GAG CAA TTC 5184 Ser His Leu Pro Tyr Ile Glu Gln Gly Met Gl - #n Leu Ala Glu Gln Phe 1715 - # 1720 - # 1725 - - AAG CAG AAA GCG CTC GGG TTA CTG CAA ACA GC - #C ACC AAA CAA GCG GAG 5232 Lys Gln Lys Ala Leu Gly Leu Leu Gln Thr Al - #a Thr Lys Gln Ala Glu 1730 - # 1735 - # 1740 - - GCT GCT GCT CCC GTG GTG GAG TCC AAG TGG CG - #A GCC CTT GAG ACA TTC 5280 Ala Ala Ala Pro Val Val Glu Ser Lys Trp Ar - #g Ala Leu Glu Thr Phe 1745 1750 - # 1755 - # 1760 - - TGG GCG AAG CAC ATG TGG AAT TTC ATC AGC GG - #G ATA CAG TAC TTA GCA 5328 Trp Ala Lys His Met Trp Asn Phe Ile Ser Gl - #y Ile Gln Tyr Leu Ala 1765 - # 1770 - # 1775 - - GGC TTA TCC ACT CTG CCT GGG AAC CCC GCA AT - #A GCA TCA TTG ATG GCA 5376 Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Il - #e Ala Ser Leu Met Ala 1780 - # 1785 - # 1790 - - TTC ACA GCC TCT ATC ACC AGC CCG CTC ACC AC - #C CAA AGT ACC CTC CTG 5424 Phe Thr Ala Ser Ile Thr Ser Pro Leu Thr Th - #r Gln Ser Thr Leu Leu 1795 - # 1800 - # 1805 - - TTT AAC ATC TTG GGG GGG TGG GTG GCT GCC CA - #A CTC GCC CCC CCC AGC 5472 Phe Asn Ile Leu Gly Gly Trp Val Ala Ala Gl - #n Leu Ala Pro Pro Ser 1810 - # 1815 - # 1820 - - GCC GCT TCG GCT TTC GTG GGC GCC GGC ATC GC - #C GGT GCG GCT GTT GGC 5520 Ala Ala Ser Ala Phe Val Gly Ala Gly Ile Al - #a Gly Ala Ala Val Gly 1825 1830 - # 1835 - # 1840 - - AGC ATA GGC CTT GGG AAG GTG CTT GTG GAC AT - #T CTG GCG GGT TAT GGA 5568 Ser Ile Gly Leu Gly Lys Val Leu Val Asp Il - #e Leu Ala Gly Tyr Gly 1845 - # 1850 - # 1855 - - GCA GGA GTG GCC GGC GCG CTC GTG GCC TTT AA - #G GTC ATG AGC GGC GAG 5616 Ala Gly Val Ala Gly Ala Leu Val Ala Phe Ly - #s Val Met Ser Gly Glu 1860 - # 1865 - # 1870 - - ATG CCC TCC ACC GAG GAC CTG GTC AAT CTA CT - #T CCT GCC ATC CTC TCT 5664 Met Pro Ser Thr Glu Asp Leu Val Asn Leu Le - #u Pro Ala Ile Leu Ser 1875 - # 1880 - # 1885 - - CCT GGC GCC CTG GTC GTC GGG GTC GTG TGT GC - #A GCA ATA CTG CGT CGA 5712 Pro Gly Ala Leu Val Val Gly Val Val Cys Al - #a Ala Ile Leu Arg Arg 1890 - # 1895 - # 1900 - - CAC GTG GGT CCG GGA GAG GGG GCT GTG CAG TG - #G ATG AAC CGG CTG ATA 5760 His Val Gly Pro Gly Glu Gly Ala Val Gln Tr - #p Met Asn Arg Leu Ile 1905 1910 - # 1915 - # 1920 - - GCG TTC GCC TCG CGG GGT AAT CAT GTT TCC CC - #C ACG CAC TAT GTG CCT 5808 Ala Phe Ala Ser Arg Gly Asn His Val Ser Pr - #o Thr His Tyr Val Pro 1925 - # 1930 - # 1935 - - GAG AGC GAC GCC GCA GCG CGT GTT ACT CAG AT - #C CTC TCC AGC CTT ACC 5856 Glu Ser Asp Ala Ala Ala Arg Val Thr Gln Il - #e Leu Ser Ser Leu Thr 1940 - # 1945 - # 1950 - - ATC ACT CAG CTG CTG AAA AGG CTC CAC CAG TG - #G ATT AAT GAA GAC TGC 5904 Ile Thr Gln Leu Leu Lys Arg Leu His Gln Tr - #p Ile Asn Glu Asp Cys 1955 - # 1960 - # 1965 - - TCC ACA CCG TGT TCC GGC TCG TGG CTA AGG GA - #T GTT TGG GAC TGG ATA 5952 Ser Thr Pro Cys Ser Gly Ser Trp Leu Arg As - #p Val Trp Asp Trp Ile 1970 - # 1975 - # 1980 - - TGC ACG GTG TTG ACT GAC TTC AAG ACC TGG CT - #C CAG TCC AAG CTC CTG 6000 Cys Thr Val Leu Thr Asp Phe Lys Thr Trp Le - #u Gln Ser Lys Leu Leu 1985 1990 - # 1995 - # 2000 - - CCG CAG CTA CCT GGA GTC CCT TTT TTC TCG TG - #C CAA CGC GGG TAC AAG 6048 Pro Gln Leu Pro Gly Val Pro Phe Phe Ser Cy - #s Gln Arg Gly Tyr Lys 2005 - # 2010 - # 2015 - - GGA GTC TGG CGG GGA GAC GGC ATC ATG CAA AC - #C ACC TGC CCA TGT GGA 6096 Gly Val Trp Arg Gly Asp Gly Ile Met Gln Th - #r Thr Cys Pro Cys Gly 2020 - # 2025 - # 2030 - - GCA CAG ATC ACC GGA CAT GTC AAA AAC GGT TC - #C ATG AGG ATC GTC GGG 6144 Ala Gln Ile Thr Gly His Val Lys Asn Gly Se - #r Met Arg Ile Val Gly 2035 - # 2040 - # 2045 - - CCT AAG ACC TGC AGC AAC ACG TGG CAT GGA AC - #A TTC CCC ATC AAC GCA 6192 Pro Lys Thr Cys Ser Asn Thr Trp His Gly Th - #r Phe Pro Ile Asn Ala 2050 - # 2055 - # 2060 - - TAC ACC ACG GGC CCC TGC ACA CCC TCT CCA GC - #G CCA AAC TAT TCT AGG 6240 Tyr Thr Thr Gly Pro Cys Thr Pro Ser Pro Al - #a Pro Asn Tyr Ser Arg 2065 2070 - # 2075 - # 2080 - - GCG CTG TGG CGG GTG GCC GCT GAG GAG TAC GT - #G GAG GTC ACG CGG GTG 6288 Ala Leu Trp Arg Val Ala Ala Glu Glu Tyr Va - #l Glu Val Thr Arg Val 2085 - # 2090 - # 2095 - - GGG GAT TTC CAC TAC GTG ACG GGC ATG ACC AC - #T GAC AAC GTA AAG TGC 6336 Gly Asp Phe His Tyr Val Thr Gly Met Thr Th - #r Asp Asn Val Lys Cys 2100 - # 2105 - # 2110 - - CCA TGC CAG GTT CCG GCT CCT GAA TTC TTC TC - #G GAG GTG GAC GGA GTG 6384 Pro Cys Gln Val Pro Ala Pro Glu Phe Phe Se - #r Glu Val Asp Gly Val 2115 - # 2120 - # 2125 - - CGG TTG CAC AGG TAC GCT CCG GCG TGC AGG CC - #T CTC CTA CGG GAG GAG 6432 Arg Leu His Arg Tyr Ala Pro Ala Cys Arg Pr - #o Leu Leu Arg Glu Glu 2130 - # 2135 - # 2140 - - GTT ACA TTC CAG GTC GGG CTC AAC CAA TAC CT - #G GTT GGG TCA CAG CTA 6480 Val Thr Phe Gln Val Gly Leu Asn Gln Tyr Le - #u Val Gly Ser Gln Leu 2145 2150 - # 2155 - # 2160 - - CCA TGC GAG CCC GAA CCG GAT GTA GCA GTG CT - #C ACT TCC ATG CTC ACC 6528 Pro Cys Glu Pro Glu Pro Asp Val Ala Val Le - #u Thr Ser Met Leu Thr 2165 - # 2170 - # 2175 - - GAC CCC TCC CAC ATC ACA GCA GAA ACG GCT AA - #G CGT AGG TTG GCC AGG 6576 Asp Pro Ser His Ile Thr Ala Glu Thr Ala Ly - #s Arg Arg Leu Ala Arg 2180 - # 2185 - # 2190 - - GGG TCT CCC CCC TCC TTG GCC AGC TCT TCA GC - #T AGC CAG TTG TCT GCG 6624 Gly Ser Pro Pro Ser Leu Ala Ser Ser Ser Al - #a Ser Gln Leu Ser Ala 2195 - # 2200 - # 2205 - - CCT TCC TTG AAG GCG ACA TGC ACT ACC CAC CA - #T GTC TCT CCG GAC GCT 6672 Pro Ser Leu Lys Ala Thr Cys Thr Thr His Hi - #s Val Ser Pro Asp Ala 2210 - # 2215 - # 2220 - - GAC CTC ATC GAG GCC AAC CTC CTG TGG CGG CA - #G GAG ATG GGC GGG AAC 6720 Asp Leu Ile Glu Ala Asn Leu Leu Trp Arg Gl - #n Glu Met Gly Gly Asn 2225 2230 - # 2235 - # 2240 - - ATC ACC CGC GTG GAG TCG GAG AAC AAG GTG GT - #A GTC CTG GAC TCT TTC 6768 Ile Thr Arg Val Glu Ser Glu Asn Lys Val Va - #l Val Leu Asp Ser Phe 2245 - # 2250 - # 2255 - - GAC CCG CTT CGA GCG GAG GAG GAT GAG AGG GA - #A GTA TCC GTT CCG GCG 6816 Asp Pro Leu Arg Ala Glu Glu Asp Glu Arg Gl - #u Val Ser Val Pro Ala 2260 - # 2265 - # 2270 - - GAG ATC CTG CGG AAA TCC AAG AAG TTC CCC GC - #A GCG ATG CCC ATC TGG 6864 Glu Ile Leu Arg Lys Ser Lys Lys Phe Pro Al - #a Ala Met Pro Ile Trp 2275 - # 2280 - # 2285 - - GCG CGC CCG GAT TAC AAC CCT CCA CTG TTA GA - #G TCC TGG AAG GAC CCG 6912 Ala Arg Pro Asp Tyr Asn Pro Pro Leu Leu Gl - #u Ser Trp Lys Asp Pro 2290 - # 2295 - # 2300 - - GAC TAC GTC CCT CCG GTG GTG CAC GGG TGC CC - #G TTG CCA CCT ATC AAG 6960 Asp Tyr Val Pro Pro Val Val His Gly Cys Pr - #o Leu Pro Pro Ile Lys 2305 2310 - # 2315 - # 2320 - - GCC CCT CCA ATA CCA CCT CCA CGG AGA AAG AG - #G ACG GTT GTC CTA ACA 7008 Ala Pro Pro Ile Pro Pro Pro Arg Arg Lys Ar - #g Thr Val Val Leu Thr 2325 - # 2330 - # 2335 - - GAG TCC TCC GTG TCT TCT GCC TTA GCG GAG CT - #C GCT ACT AAG ACC TTC 7056 Glu Ser Ser Val Ser Ser Ala Leu Ala Glu Le - #u Ala Thr Lys Thr Phe 2340 - # 2345 - # 2350 - - GGC AGC TCC GAA TCA TCG GCC GTC GAC AGC GG - #C ACG GCG ACC GCC CTT 7104 Gly Ser Ser Glu Ser Ser Ala Val Asp Ser Gl - #y Thr Ala Thr Ala Leu 2355 - # 2360 - # 2365 - - CCT GAC CAG GCC TCC GAC GAC GGT GAC AAA GG - #A TCC GAC GTT GAG TCG 7152 Pro Asp Gln Ala Ser Asp Asp Gly Asp Lys Gl - #y Ser Asp Val Glu Ser 2370 - # 2375 - # 2380 - - TAC TCC TCC ATG CCC CCC CTT GAG GGG GAA CC - #G GGG GAC CCC GAT CTC 7200 Tyr Ser Ser Met Pro Pro Leu Glu Gly Glu Pr - #o Gly Asp Pro Asp Leu 2385 2390 - # 2395 - # 2400 - - AGT GAC GGG TCT TGG TCT ACC GTG AGC GAG GA - #A GCT AGT GAG GAT GTC 7248 Ser Asp Gly Ser Trp Ser Thr Val Ser Glu Gl - #u Ala Ser Glu Asp Val 2405 - # 2410 - # 2415 - - GTC TGC TGC TCA ATG TCC TAC ACA TGG ACA GG - #C GCC TTG ATC ACG CCA 7296 Val Cys Cys Ser Met Ser Tyr Thr Trp Thr Gl - #y Ala Leu Ile Thr Pro 2420 - # 2425 - # 2430 - - TGC GCT GCG GAG GAA AGC AAG CTG CCC ATC AA - #C GCG TTG AGC AAC TCT 7344 Cys Ala Ala Glu Glu Ser Lys Leu Pro Ile As - #n Ala Leu Ser Asn Ser 2435 - # 2440 - # 2445 - - TTG CTG CGC CAC CAT AAC ATG GTT TAT GCC AC - #A ACA TCT CGC AGC GCA 7392 Leu Leu Arg His His Asn Met Val Tyr Ala Th - #r Thr Ser Arg Ser Ala 2450 - # 2455 - # 2460 - - GGC CTG CGG CAG AAG AAG GTC ACC TTT GAC AG - #A CTG CAA GTC CTG GAC 7440 Gly Leu Arg Gln Lys Lys Val Thr Phe Asp Ar - #g Leu Gln Val Leu Asp 2465 2470 - # 2475 - # 2480 - - GAC CAC TAC CGG GAC GTG CTC AAG GAG ATG AA - #G GCG AAG GCG TCC ACA 7488 Asp His Tyr Arg Asp Val Leu Lys Glu Met Ly - #s Ala Lys Ala Ser Thr 2485 - # 2490 - # 2495 - - GTT AAG GCT AAA CTC CTA TCC GTA GAG GAA GC - #C TGC AAG CTG ACG CCC 7536 Val Lys Ala Lys Leu Leu Ser Val Glu Glu Al - #a Cys Lys Leu Thr Pro 2500 - # 2505 - # 2510 - - CCA CAT TCG GCC AAA TCC AAG TTT GGC TAT GG - #G GCA AAG GAC GTC CGG 7584 Pro His Ser Ala Lys Ser Lys Phe Gly Tyr Gl - #y Ala Lys Asp Val Arg 2515 - # 2520 - # 2525 - - AAC CTA TCC AGC AAG GCC GTT AAC CAC ATC CA - #C TCC GTG TGG AAG GAC 7632 Asn Leu Ser Ser Lys Ala Val Asn His Ile Hi - #s Ser Val Trp Lys Asp 2530 - # 2535 - # 2540 - - TTG CTG GAA GAC ACT GTG ACA CCA ATT GAC AC - #C ACC ATC ATG GCA AAA 7680 Leu Leu Glu Asp Thr Val Thr Pro Ile Asp Th - #r Thr Ile Met Ala Lys 2545 2550 - # 2555 - # 2560 - - AAT GAG GTT TTC TGT GTC CAA CCA GAG AAA GG - #A GGC CGT AAG CCA GCC 7728 Asn Glu Val Phe Cys Val Gln Pro Glu Lys Gl - #y Gly Arg Lys Pro Ala 2565 - # 2570 - # 2575 - - CGC CTT ATC GTA TTC CCA GAT CTG GGA GTC CG - #T GTA TGC GAG AAG ATG 7776 Arg Leu Ile Val Phe Pro Asp Leu Gly Val Ar - #g Val Cys Glu Lys Met 2580 - # 2585 - # 2590 - - GCC CTC TAT GAT GTG GTC TCC ACC CTT CCT CA - #G GTC GTG ATG GGC TCC 7824 Ala Leu Tyr Asp Val Val Ser Thr Leu Pro Gl - #n Val Val Met Gly Ser 2595 - # 2600 - # 2605 - - TCA TAC GGA TTC CAG TAC TCT CCT GGG CAG CG - #A GTC GAG TTC CTG GTG 7872 Ser Tyr Gly Phe Gln Tyr Ser Pro Gly Gln Ar - #g Val Glu Phe Leu Val 2610 - # 2615 - # 2620 - - AAT ACC TGG AAA TCA AAG AAA AAC CCC ATG GG - #C TTT TCA TAT GAC ACT 7920 Asn Thr Trp Lys Ser Lys Lys Asn Pro Met Gl - #y Phe Ser Tyr Asp Thr 2625 2630 - # 2635 - # 2640 - - CGC TGT TTC GAC TCA ACG GTC ACC GAG AAC GA - #C ATC CGT GTT GAG GAG 7968 Arg Cys Phe Asp Ser Thr Val Thr Glu Asn As - #p Ile Arg Val Glu Glu 2645 - # 2650 - # 2655 - - TCA ATT TAC CAA TGT TGT GAC TTG GCC CCC GA - #A GCC AGA CAG GCC ATA 8016 Ser Ile Tyr Gln Cys Cys Asp Leu Ala Pro Gl - #u Ala Arg Gln Ala Ile 2660 - # 2665 - # 2670 - - AAA TCG CTC ACA GAG CGG CTT TAT ATC GGG GG - #T CCT CTG ACT AAT TCA 8064 Lys Ser Leu Thr Glu Arg Leu Tyr Ile Gly Gl - #y Pro Leu Thr Asn Ser 2675 - # 2680 - # 2685 - - AAA GGG CAG AAC TGC GGT TAT CGC CGG TGC CG - #C GCG AGC GGC GTG CTG 8112 Lys Gly Gln Asn Cys Gly Tyr Arg Arg Cys Ar - #g Ala Ser Gly Val Leu 2690 - # 2695 - # 2700 - - ACG ACT AGC TGC GGT AAC ACC CTC ACA TGT TA - #C TTG AAG GCC TCT GCA 8160 Thr Thr Ser Cys Gly Asn Thr Leu Thr Cys Ty - #r Leu Lys Ala Ser Ala 2705 2710 - # 2715 - # 2720 - - GCC TGT CGA GCT GCG AAG CTC CAG GAC TGC AC - #G ATG CTC GTG AAC GGA 8208 Ala Cys Arg Ala Ala Lys Leu Gln Asp Cys Th - #r Met Leu Val Asn Gly 2725 - # 2730 - # 2735 - - GAC GAC CTC GTC GTT ATC TGT GAA AGC GCG GG - #A ACC CAA GAG GAC GCG 8256 Asp Asp Leu Val Val Ile Cys Glu Ser Ala Gl - #y Thr Gln Glu Asp Ala 2740 - # 2745 - # 2750 - - GCG AGC CTA CGA GTC TTC ACG GAG GCT ATG AC - #T AGG TAC TCC GCC CCC 8304 Ala Ser Leu Arg Val Phe Thr Glu Ala Met Th - #r Arg Tyr Ser Ala Pro 2755 - # 2760 - # 2765 - - CCC GGG GAC CCG CCC CAA CCA GAA TAC GAC TT - #G GAG CTG ATA ACA TCA 8352 Pro Gly Asp Pro Pro Gln Pro Glu Tyr Asp Le - #u Glu Leu Ile Thr Ser 2770 - # 2775 - # 2780 - - TGT TCC TCC AAT GTG TCG GTC GCC CAC GAT GC - #A TCA GGC AAA AGG GTG 8400 Cys Ser Ser Asn Val Ser Val Ala His Asp Al - #a Ser Gly Lys Arg Val 2785 2790 - # 2795 - # 2800 - - TAC TAC CTC ACC CGT GAT CCC ACC ACC CCC CT - #A GCA CGG GCT GCG TGG 8448 Tyr Tyr Leu Thr Arg Asp Pro Thr Thr Pro Le - #u Ala Arg Ala Ala Trp 2805 - # 2810 - # 2815 - - GAG ACA GCT AGA CAC ACT CCA GTT AAC TCC TG - #G CTA GGC AAC ATT ATT 8496 Glu Thr Ala Arg His Thr Pro Val Asn Ser Tr - #p Leu Gly Asn Ile Ile 2820 - # 2825 - # 2830 - - ATG TAT GCG CCC ACT TTG TGG GCA AGG ATG AT - #T CTG ATG ACT CAC TTC 8544 Met Tyr Ala Pro Thr Leu Trp Ala Arg Met Il - #e Leu Met Thr His Phe 2835 - # 2840 - # 2845 - - TTC TCC ATC CTT CTA GCG CAG GAG CAA CTT GA - #A AAA GCC CTG GAC TGC 8592 Phe Ser Ile Leu Leu Ala Gln Glu Gln Leu Gl - #u Lys Ala Leu Asp Cys 2850 - # 2855 - # 2860 - - CAG ATC TAC GGG GCC TGT TAC TCC ATT GAG CC - #A CTT GAC CTA CCT CAG 8640 Gln Ile Tyr Gly Ala Cys Tyr Ser Ile Glu Pr - #o Leu Asp Leu Pro Gln 2865 2870 - # 2875 - # 2880 - - ATC ATT GAA CGA CTC CAT GGC CTT AGC GCA TT - #T TCA CTC CAT AGT TAC 8688 Ile Ile Glu Arg Leu His Gly Leu Ser Ala Ph - #e Ser Leu His Ser Tyr 2885 - # 2890 - # 2895 - - TCT CCA GGT GAG ATC AAT AGG GTG GCT TCA TG - #C CTC AGG AAA CTT GGG 8736 Ser Pro Gly Glu Ile Asn Arg Val Ala Ser Cy - #s Leu Arg Lys Leu Gly 2900 - # 2905 - # 2910 - - GTA CCA CCC TTG CGA GTC TGG AGA CAT CGG GC - #C AGG AGC GTC CGC GCT 8784 Val Pro Pro Leu Arg Val Trp Arg His Arg Al - #a Arg Ser Val Arg Ala 2915 - # 2920 - # 2925 - - AGG CTA CTG TCC CAG GGA GGG AGG GCC GCC AC - #T TGT GGC AAA TAC CTC 8832 Arg Leu Leu Ser Gln Gly Gly Arg Ala Ala Th - #r Cys Gly Lys Tyr Leu 2930 - # 2935 - # 2940 - - TTC AAC TGG GCA GTA AAA ACC AAA CTT AAA CT - #C ACT CCA ATC CCG GCT 8880 Phe Asn Trp Ala Val Lys Thr Lys Leu Lys Le - #u Thr Pro Ile Pro Ala 2945 2950 - # 2955 - # 2960 - - GCG TCC CGG CTG GAC TTG TCC GGC TGG TTC GT - #T GCT GGT TAC AGC GGG 8928 Ala Ser Arg Leu Asp Leu Ser Gly Trp Phe Va - #l Ala Gly Tyr Ser Gly 2965 - # 2970 - # 2975 - - GGA GAC ATA TAT CAC AGC CTG TCT CGT GCC CG - #A CCC CGT TGG TTC ATG 8976 Gly Asp Ile Tyr His Ser Leu Ser Arg Ala Ar - #g Pro Arg Trp Phe Met 2980 - # 2985 - # 2990 - - CTG TGC CTA CTC CTA CTT TCT GTA GGG GTA GG - #C ATC TAC CTG CTC CCC 9024 Leu Cys Leu Leu Leu Leu Ser Val Gly Val Gl - #y Ile Tyr Leu Leu Pro 2995 - # 3000 - # 3005 - - AAC CGA - # - # -# 9030 Asn Arg 3010 - - - - (2) INFORMATION FOR SEQ ID NO:14: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3010 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14: - - Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Th - #r Lys Arg Asn ThrAsn 1 5 - # 10 - # 15 - - Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gl - #y Gly Gln Ile Val Gly 20 - # 25 - # 30 - - Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Ar - #g Leu Gly Val Arg Ala 35 - # 40 - # 45 - - Pro Arg Lys Thr Ser Glu Arg Ser Gln Pro Ar - #g Gly Arg Arg Gln Pro 50 - # 55 - # 60 - - Ile Pro Lys Ala Arg Arg Pro Glu Gly Arg Th - #r Trp Ala Gln Pro Gly 65 - # 70 - # 75 - # 80 - - Tyr Pro Trp Pro Leu Tyr Gly Asn Glu Gly Le - #u Gly Trp Ala Gly Trp 85 - # 90 - # 95 - - Leu Leu Ser Pro Arg Gly Ser Arg Pro Ser Tr - #p Gly Pro Thr Asp Pro 100 - # 105 - # 110 - - Arg Arg Arg Ser Arg Asn Leu Gly Lys Val Il - #e Asp Thr Leu Thr Cys 115 - # 120 - # 125 - - Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Le - #u Val Gly Ala Pro Leu 130 - # 135 - # 140 - - Gly Gly Ala Ala Arg Ala Leu Ala His Gly Va - #l Arg Val Leu Glu Asp 145 1 - #50 1 - #55 1 -#60 - - Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gl - #y Cys Ser Phe SerIle 165 - # 170 - # 175 - - Phe Leu Leu Ala Leu Leu Ser Cys Leu Thr Th - #r Pro Ala Ser Ala Tyr 180 - # 185 - # 190 - - Glu Val His Asn Val Ser Gly Ile Tyr His Va - #l Thr Asn Asp Cys Ser 195 - # 200 - # 205 - - Asn Ala Ser Ile Val Tyr Glu Ala Ala Asp Le - #u Ile Met His Thr Pro 210 - # 215 - # 220 - - Gly Cys Val Pro Cys Val Arg Glu Gly Asn Se - #r Ser Arg Cys Trp Val 225 2 - #30 2 - #35 2 -#40 - - Ala Leu Thr Pro Thr Leu Ala Ala Arg Asn Va - #l Thr Ile Pro ThrThr 245 - # 250 - # 255 - - Thr Ile Arg Arg His Val Asp Leu Leu Val Gl - #y Ala Ala Ala Phe Cys 260 - # 265 - # 270 - - Ser Ala Met Tyr Val Gly Asp Leu Cys Gly Se - #r Val Phe Leu Val Ser 275 - # 280 - # 285 - - Gln Leu Phe Thr Phe Ser Pro Arg Arg His Va - #l Thr Leu Gln Asp Cys 290 - # 295 - # 300 - - Asn Cys Ser Ile Tyr Pro Gly His Val Ser Gl - #y His Arg Met Ala Trp 305 3 - #10 3 - #15 3 -#20 - - Asp Met Met Met Asn Trp Ser Pro Thr Thr Al - #a Leu Val Val SerGln 325 - # 330 - # 335 - - Leu Leu Arg Ile Pro Gln Ala Val Val Asp Me - #t Val Ala Gly Ala His 340 - # 345 - # 350 - - Trp Gly Val Leu Ala Gly Leu Ala Tyr Tyr Se - #r Met Ala Gly Asn Trp 355 - # 360 - # 365 - - Ala Lys Val Leu Ile Val Met Leu Leu Phe Al - #a Gly Val Asp Gly Asp 370 - # 375 - # 380 - - Thr His Val Thr Gly Gly Ala Gln Ala Lys Th - #r Thr Asn Arg Leu Val 385 3 - #90 3 - #95 4 -#00 - - Ser Met Phe Ala Ser Gly Pro Ser Gln Lys Il - #e Gln Leu Ile AsnThr 405 - # 410 - # 415 - - Asn Gly Ser Trp His Ile Asn Arg Thr Ala Le - #u Asn Cys Asn Asp Ser 420 - # 425 - # 430 - - Leu Gln Thr Gly Phe Leu Ala Ala Leu Phe Ty - #r Thr His Ser Phe Asn 435 - # 440 - # 445 - - Ser Ser Gly Cys Pro Glu Arg Met Ala Gln Cy - #s Arg Thr Ile Asp Lys 450 - # 455 - # 460 - - Phe Asp Gln Gly Trp Gly Pro Ile Thr Tyr Al - #a Glu Ser Ser Arg Ser 465 4 - #70 4 - #75 4 -#80 - - Asp Gln Arg Pro Tyr Cys Trp His Tyr Pro Pr - #o Pro Gln Cys ThrIle 485 - # 490 - # 495 - - Val Pro Ala Ser Glu Val Cys Gly Pro Val Ty - #r Cys Phe Thr Pro Ser 500 - # 505 - # 510 - - Pro Val Val Val Gly Thr Thr Asp Arg Phe Gl - #y Val Pro Thr Tyr Arg 515 - # 520 - # 525 - - Trp Gly Glu Asn Glu Thr Asp Val Leu Leu Le - #u Asn Asn Thr Arg Pro 530 - # 535 - # 540 - - Pro Gln Gly Asn Trp Phe Gly Cys Thr Trp Me - #t Asn Ser Thr Gly Phe 545 5 - #50 5 - #55 5 -#60 - - Thr Lys Thr Cys Gly Gly Pro Pro Cys Asn Il - #e Gly Gly Val GlyAsn 565 - # 570 - # 575 - - Asn Thr Leu Thr Cys Pro Thr Asp Cys Phe Ar - #g Lys His Pro Glu Ala 580 - # 585 - # 590 - - Thr Tyr Thr Lys Cys Gly Ser Gly Pro Trp Le - #u Thr Pro Arg Cys Met 595 - # 600 - # 605 - - Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pr - #o Cys Thr Val Asn Phe 610 - # 615 - # 620 - - Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gl - #y Val Glu His Arg Leu 625 6 - #30 6 - #35 6 -#40 - - Asn Ala Ala Cys Asn Trp Thr Arg Gly Glu Ar - #g Cys Asp Leu GluAsp 645 - # 650 - # 655 - - Arg Asp Arg Pro Glu Leu Ser Pro Leu Leu Le - #u Ser Thr Thr Glu Trp 660 - # 665 - # 670 - - Gln Val Leu Pro Cys Ser Phe Thr Thr Leu Pr - #o Ala Leu Ser Thr Gly 675 - # 680 - # 685 - - Leu Ile His Leu His Gln Asn Ile Val Asp Va - #l Gln Tyr Leu Tyr Gly 690 - # 695 - # 700 - - Ile Gly Ser Ala Val Val Ser Phe Ala Ile Ly - #s Trp Glu Tyr Val Leu 705 7 - #10 7 - #15 7 -#20 - - Leu Leu Phe Leu Leu Leu Ala Asp Ala Arg Va - #l Cys Ala Cys LeuTrp 725 - # 730 - # 735 - - Met Met Leu Leu Ile Ala Gln Ala Glu Ala Al - #a Leu Glu Asn Leu Val 740 - # 745 - # 750 - - Val Leu Asn Ser Ala Ser Val Ala Gly Ala Hi - #s Gly Ile Leu Ser Phe 755 - # 760 - # 765 - - Leu Val Phe Phe Cys Ala Ala Trp Tyr Ile Ly - #s Gly Arg Leu Val Pro 770 - # 775 - # 780 - - Gly Ala Thr Tyr Ala Leu Tyr Gly Val Trp Pr - #o Leu Leu Leu Leu Leu 785 7 - #90 7 - #95 8 -#00 - - Leu Ala Leu Pro Pro Arg Ala Tyr Ala Met As - #p Arg Glu Met AlaAla 805 - # 810 - # 815 - - Ser Cys Gly Gly Ala Val Phe Val Gly Leu Va - #l Leu Leu Thr Leu Ser 820 - # 825 - # 830 - - Pro Tyr Tyr Lys Val Phe Leu Ala Arg Leu Il - #e Trp Trp Leu Gln Tyr 835 - # 840 - # 845 - - Phe Thr Thr Arg Ala Glu Ala Asp Leu His Va - #l Trp Ile Pro Pro Leu 850 - # 855 - # 860 - - Asn Ala Arg Gly Gly Arg Asp Ala Ile Ile Le - #u Leu Met Cys Ala Val 865 8 - #70 8 - #75 8 -#80 - - His Pro Glu Leu Ile Phe Asp Ile Thr Lys Le - #u Leu Ile Ala IleLeu 885 - # 890 - # 895 - - Gly Pro Leu Met Val Leu Gln Ala Gly Ile Th - #r Arg Val Pro Tyr Phe 900 - # 905 - # 910 - - Val Arg Ala Gln Gly Leu Ile His Ala Cys Me - #t Leu Val Arg Lys Val 915 - # 920 - # 925 - - Ala Gly Gly His Tyr Val Gln Met Ala Phe Me - #t Lys Leu Gly Ala Leu 930 - # 935 - # 940 - - Thr Gly Thr Tyr Ile Tyr Asn His Leu Thr Pr - #o Leu Arg Asp Trp Pro 945 9 - #50 9 - #55 9 -#60 - - Arg Ala Gly Leu Arg Asp Leu Ala Val Ala Va - #l Glu Pro Val ValPhe 965 - # 970 - # 975 - - Ser Asp Met Glu Thr Lys Ile Ile Thr Trp Gl - #y Ala Asp Thr Ala Ala 980 - # 985 - # 990 - - Cys Gly Asp Ile Ile Leu Gly Leu Pro Val Se - #r Ala Arg Arg Gly Lys 995 - # 1000 - # 1005 - - Glu Ile Leu Leu Gly Pro Ala Asp Ser Leu Gl - #u Gly Arg Gly Leu Arg 1010 - # 1015 - # 1020 - - Leu Leu Ala Pro Ile Thr Ala Tyr Ser Gln Gl - #n Thr Arg Gly Leu Leu 1025 1030 - # 1035 - # 1040 - - Gly Cys Ile Ile Thr Ser Leu Thr Gly Arg As - #p Lys Asn Gln Val Glu 1045 - # 1050 - # 1055 - - Gly Glu Val Gln Val Val Ser Thr Ala Thr Gl - #n Ser Phe Leu Ala Thr 1060 - # 1065 - # 1070 - - Cys Val Asn Gly Val Cys Trp Thr Val Tyr Hi - #s Gly Ala Gly Ser Lys 1075 - # 1080 - # 1085 - - Thr Leu Ala Ala Pro Lys Gly Pro Ile Thr Gl - #n Met Tyr Thr Asn Val 1090 - # 1095 - # 1100 - - Asp Gln Asp Leu Val Gly Trp Pro Lys Pro Pr - #o Gly Ala Arg Ser Leu 1105 1110 - # 1115 - # 1120 - - Thr Pro Cys Thr Cys Gly Ser Ser Asp Leu Ty - #r Leu Val Thr Arg His 1125 - # 1130 - # 1135 - - Ala Asp Val Ile Pro Val Arg Arg Arg Gly As - #p Ser Arg Gly Ser Leu 1140 - # 1145 - # 1150 - - Leu Ser Pro Arg Pro Val Ser Tyr Leu Lys Gl - #y Ser Ser Gly Gly Pro 1155 - # 1160 - # 1165 - - Leu Leu Cys Pro Phe Gly His Ala Val Gly Il - #e Phe Arg Ala Ala Val 1170 - # 1175 - # 1180 - - Cys Thr Arg Gly Val Ala Lys Ala Val Asp Ph - #e Val Pro Val Glu Ser 1185 1190 - # 1195 - # 1200 - - Met Glu Thr Thr Met Arg Ser Pro Val Phe Th - #r Asp Asn Ser Ser Pro 1205 - # 1210 - # 1215 - - Pro Ala Val Pro Gln Ser Phe Gln Val Ala Hi - #s Leu His Ala Pro Thr 1220 - # 1225 - # 1230 - - Gly Ser Gly Lys Ser Thr Lys Val Pro Ala Al - #a Tyr Ala Ala Gln Gly 1235 - # 1240 - # 1245 - - Tyr Lys Val Leu Val Leu Asn Pro Ser Val Al - #a Ala Thr Leu Gly Phe 1250 - # 1255 - # 1260 - - Gly Ala Tyr Met Ser Lys Ala His Gly Ile As - #p Pro Asn Ile Arg Thr 1265 1270 - # 1275 - # 1280 - - Gly Val Arg Thr Ile Thr Thr Gly Ala Pro Va - #l Thr Tyr Ser Thr Tyr 1285 - # 1290 - # 1295 - - Gly Lys Phe Leu Ala Asp Gly Gly Cys Ser Gl - #y Gly Ala Tyr Asp Ile 1300 - # 1305 - # 1310 - - Ile Ile Cys Asp Glu Cys His Ser Thr Asp Se - #r Thr Thr Ile Leu Gly 1315 - # 1320 - # 1325 - - Ile Gly Thr Val Leu Asp Gln Ala Glu Thr Al - #a Gly Ala Arg Leu Val 1330 - # 1335 - # 1340 - - Val Leu Ala Thr Ala Thr Pro Pro Gly Ser Va - #l Thr Val Pro His Pro 1345 1350 - # 1355 - # 1360 - - Asn Ile Glu Glu Val Ala Leu Ser Asn Thr Gl - #y Glu Ile Pro Phe Tyr 1365 - # 1370 - # 1375 - - Gly Lys Ala Ile Pro Ile Glu Ala Ile Arg Gl - #y Gly Arg His Leu Ile 1380 - # 1385 - # 1390 - - Phe Cys His Ser Lys Lys Lys Cys Asp Glu Le - #u Ala Ala Lys Leu Ser 1395 - # 1400 - # 1405 - - Gly Leu Gly Ile Asn Ala Val Ala Tyr Tyr Ar - #g Gly Leu Asp Val Ser 1410 - # 1415 - # 1420 - - Val Ile Pro Thr Ile Gly Asp Val Val Val Va - #l Ala Thr Asp Ala Leu 1425 1430 - # 1435 - # 1440 - - Met Thr Gly Tyr Thr Gly Asp Phe Asp Ser Va - #l Ile Asp Cys Asn Thr 1445 - # 1450 - # 1455 - - Cys Val Thr Gln Thr Val Asp Phe Ser Leu As - #p Pro Thr Phe Thr Ile 1460 - # 1465 - # 1470 - - Glu Thr Thr Thr Val Pro Gln Asp Ala Val Se - #r Arg Ser Gln Arg Arg 1475 - # 1480 - # 1485 - - Gly Arg Thr Gly Arg Gly Arg Arg Gly Ile Ty - #r Arg Phe Val Thr Pro 1490 - # 1495 - # 1500 - - Gly Glu Arg Pro Ser Gly Met Phe Asp Ser Se - #r Val Leu Cys Glu Cys 1505 1510 - # 1515 - # 1520 - - Tyr Asp Ala Gly Cys Ala Trp Tyr Glu Leu Th - #r Pro Ala Glu Thr Ser 1525 - # 1530 - # 1535 - - Val Arg Leu Arg Ala Tyr Leu Asn Thr Pro Gl - #y Leu Pro Val Cys Gln 1540 - # 1545 - # 1550 - - Asp His Leu Glu Phe Trp Glu Ser Val Phe Th - #r Gly Leu Thr His Ile 1555 - # 1560 - # 1565 - - Asp Ala His Phe Leu Ser Gln Thr Lys Gln Al - #a Gly Asp Asn Phe Pro 1570 - # 1575 - # 1580 - - Tyr Leu Val Ala Tyr Gln Ala Thr Val Cys Al - #a Arg Ala Gln Ala Pro 1585 1590 - # 1595 - # 1600 - - Pro Pro Ser Trp Asp Gln Met Trp Lys Cys Le - #u Ile Arg Leu Lys Pro 1605 - # 1610 - # 1615 - - Thr Leu His Gly Pro Thr Pro Leu Leu Tyr Ar - #g Leu Gly Ala Val Gln 1620 - # 1625 - # 1630 - - Asn Glu Val Thr Leu Thr His Pro Ile Thr Ly - #s Tyr Ile Met Ala Cys 1635 - # 1640 - # 1645 - - Met Ser Ala Asp Leu Glu Val Val Thr Ser Th - #r Trp Val Leu Val Gly 1650 - # 1655 - # 1660 - - Gly Val Leu Ala Ala Leu Ala Ala Tyr Cys Le - #u Thr Thr Gly Ser Val 1665 1670 - # 1675 - # 1680 - - Val Ile Val Gly Arg Ile Ile Leu Ser Gly Ar - #g Pro Ala Ile Val Pro 1685 - # 1690 - # 1695 - - Asp Arg Glu Leu Leu Tyr Gln Glu Phe Asp Gl - #u Met Glu Glu Cys Ala 1700 - # 1705 - # 1710 - - Ser His Leu Pro Tyr Ile Glu Gln Gly Met Gl - #n Leu Ala Glu Gln Phe 1715 - # 1720 - # 1725 - - Lys Gln Lys Ala Leu Gly Leu Leu Gln Thr Al - #a Thr Lys Gln Ala Glu 1730 - # 1735 - # 1740 - - Ala Ala Ala Pro Val Val Glu Ser Lys Trp Ar - #g Ala Leu Glu Thr Phe 1745 1750 - # 1755 - # 1760 - - Trp Ala Lys His Met Trp Asn Phe Ile Ser Gl - #y Ile Gln Tyr Leu Ala 1765 - # 1770 - # 1775 - - Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Il - #e Ala Ser Leu Met Ala 1780 - # 1785 - # 1790 - - Phe Thr Ala Ser Ile Thr Ser Pro Leu Thr Th - #r Gln Ser Thr Leu Leu 1795 - # 1800 - # 1805 - - Phe Asn Ile Leu Gly Gly Trp Val Ala Ala Gl - #n Leu Ala Pro Pro Ser 1810 - # 1815 - # 1820 - - Ala Ala Ser Ala Phe Val Gly Ala Gly Ile Al - #a Gly Ala Ala Val Gly 1825 1830 - # 1835 - # 1840 - - Ser Ile Gly Leu Gly Lys Val Leu Val Asp Il - #e Leu Ala Gly Tyr Gly 1845 - # 1850 - # 1855 - - Ala Gly Val Ala Gly Ala Leu Val Ala Phe Ly - #s Val Met Ser Gly Glu 1860 - # 1865 - # 1870 - - Met Pro Ser Thr Glu Asp Leu Val Asn Leu Le - #u Pro Ala Ile Leu Ser 1875 - # 1880 - # 1885 - - Pro Gly Ala Leu Val Val Gly Val Val Cys Al - #a Ala Ile Leu Arg Arg 1890 - # 1895 - # 1900 - - His Val Gly Pro Gly Glu Gly Ala Val Gln Tr - #p Met Asn Arg Leu Ile 1905 1910 - # 1915 - # 1920 - - Ala Phe Ala Ser Arg Gly Asn His Val Ser Pr - #o Thr His Tyr Val Pro 1925 - # 1930 - # 1935 - - Glu Ser Asp Ala Ala Ala Arg Val Thr Gln Il - #e Leu Ser Ser Leu Thr 1940 - # 1945 - # 1950 - - Ile Thr Gln Leu Leu Lys Arg Leu His Gln Tr - #p Ile Asn Glu Asp Cys 1955 - # 1960 - # 1965 - - Ser Thr Pro Cys Ser Gly Ser Trp Leu Arg As - #p Val Trp Asp Trp Ile 1970 - # 1975 - # 1980 - - Cys Thr Val Leu Thr Asp Phe Lys Thr Trp Le - #u Gln Ser Lys Leu Leu 1985 1990 - # 1995 - # 2000 - - Pro Gln Leu Pro Gly Val Pro Phe Phe Ser Cy - #s Gln Arg Gly Tyr Lys 2005 - # 2010 - # 2015 - - Gly Val Trp Arg Gly Asp Gly Ile Met Gln Th - #r Thr Cys Pro Cys Gly 2020 - # 2025 - # 2030 - - Ala Gln Ile Thr Gly His Val Lys Asn Gly Se - #r Met Arg Ile Val Gly 2035 - # 2040 - # 2045 - - Pro Lys Thr Cys Ser Asn Thr Trp His Gly Th - #r Phe Pro Ile Asn Ala 2050 - # 2055 - # 2060 - - Tyr Thr Thr Gly Pro Cys Thr Pro Ser Pro Al - #a Pro Asn Tyr Ser Arg 2065 2070 - # 2075 - # 2080 - - Ala Leu Trp Arg Val Ala Ala Glu Glu Tyr Va - #l Glu Val Thr Arg Val 2085 - # 2090 - # 2095 - - Gly Asp Phe His Tyr Val Thr Gly Met Thr Th - #r Asp Asn Val Lys Cys 2100 - # 2105 - # 2110 - - Pro Cys Gln Val Pro Ala Pro Glu Phe Phe Se - #r Glu Val Asp Gly Val 2115 - # 2120 - # 2125 - - Arg Leu His Arg Tyr Ala Pro Ala Cys Arg Pr - #o Leu Leu Arg Glu Glu 2130 - # 2135 - # 2140 - - Val Thr Phe Gln Val Gly Leu Asn Gln Tyr Le - #u Val Gly Ser Gln Leu 2145 2150 - # 2155 - # 2160 - - Pro Cys Glu Pro Glu Pro Asp Val Ala Val Le - #u Thr Ser Met Leu Thr 2165 - # 2170 - # 2175 - - Asp Pro Ser His Ile Thr Ala Glu Thr Ala Ly - #s Arg Arg Leu Ala Arg 2180 - # 2185 - # 2190 - - Gly Ser Pro Pro Ser Leu Ala Ser Ser Ser Al - #a Ser Gln Leu Ser Ala 2195 - # 2200 - # 2205 - - Pro Ser Leu Lys Ala Thr Cys Thr Thr His Hi - #s Val Ser Pro Asp Ala 2210 - # 2215 - # 2220 - - Asp Leu Ile Glu Ala Asn Leu Leu Trp Arg Gl - #n Glu Met Gly Gly Asn 2225 2230 - # 2235 - # 2240 - - Ile Thr Arg Val Glu Ser Glu Asn Lys Val Va - #l Val Leu Asp Ser Phe 2245 - # 2250 - # 2255 - - Asp Pro Leu Arg Ala Glu Glu Asp Glu Arg Gl - #u Val Ser Val Pro Ala 2260 - # 2265 - # 2270 - - Glu Ile Leu Arg Lys Ser Lys Lys Phe Pro Al - #a Ala Met Pro Ile Trp 2275 - # 2280 - # 2285 - - Ala Arg Pro Asp Tyr Asn Pro Pro Leu Leu Gl - #u Ser Trp Lys Asp Pro 2290 - # 2295 - # 2300 - - Asp Tyr Val Pro Pro Val Val His Gly Cys Pr - #o Leu Pro Pro Ile Lys 2305 2310 - # 2315 - # 2320 - - Ala Pro Pro Ile Pro Pro Pro Arg Arg Lys Ar - #g Thr Val Val Leu Thr 2325 - # 2330 - # 2335 - - Glu Ser Ser Val Ser Ser Ala Leu Ala Glu Le - #u Ala Thr Lys Thr Phe 2340 - # 2345 - # 2350 - - Gly Ser Ser Glu Ser Ser Ala Val Asp Ser Gl - #y Thr Ala Thr Ala Leu 2355 - # 2360 - # 2365 - - Pro Asp Gln Ala Ser Asp Asp Gly Asp Lys Gl - #y Ser Asp Val Glu Ser 2370 - # 2375 - # 2380 - - Tyr Ser Ser Met Pro Pro Leu Glu Gly Glu Pr - #o Gly Asp Pro Asp Leu 2385 2390 - # 2395 - # 2400 - - Ser Asp Gly Ser Trp Ser Thr Val Ser Glu Gl - #u Ala Ser Glu Asp Val 2405 - # 2410 - # 2415 - - Val Cys Cys Ser Met Ser Tyr Thr Trp Thr Gl - #y Ala Leu Ile Thr Pro 2420 - # 2425 - # 2430 - - Cys Ala Ala Glu Glu Ser Lys Leu Pro Ile As - #n Ala Leu Ser Asn Ser 2435 - # 2440 - # 2445 - - Leu Leu Arg His His Asn Met Val Tyr Ala Th - #r Thr Ser Arg Ser Ala 2450 - # 2455 - # 2460 - - Gly Leu Arg Gln Lys Lys Val Thr Phe Asp Ar - #g Leu Gln Val Leu Asp 2465 2470 - # 2475 - # 2480 - - Asp His Tyr Arg Asp Val Leu Lys Glu Met Ly - #s Ala Lys Ala Ser Thr 2485 - # 2490 - # 2495 - - Val Lys Ala Lys Leu Leu Ser Val Glu Glu Al - #a Cys Lys Leu Thr Pro 2500 - # 2505 - # 2510 - - Pro His Ser Ala Lys Ser Lys Phe Gly Tyr Gl - #y Ala Lys Asp Val Arg 2515 - # 2520 - # 2525 - - Asn Leu Ser Ser Lys Ala Val Asn His Ile Hi - #s Ser Val Trp Lys Asp 2530 - # 2535 - # 2540 - - Leu Leu Glu Asp Thr Val Thr Pro Ile Asp Th - #r Thr Ile Met Ala Lys 2545 2550 - # 2555 - # 2560 - - Asn Glu Val Phe Cys Val Gln Pro Glu Lys Gl - #y Gly Arg Lys Pro Ala 2565 - # 2570 - # 2575 - - Arg Leu Ile Val Phe Pro Asp Leu Gly Val Ar - #g Val Cys Glu Lys Met 2580 - # 2585 - # 2590 - - Ala Leu Tyr Asp Val Val Ser Thr Leu Pro Gl - #n Val Val Met Gly Ser 2595 - # 2600 - # 2605 - - Ser Tyr Gly Phe Gln Tyr Ser Pro Gly Gln Ar - #g Val Glu Phe Leu Val 2610 - # 2615 - # 2620 - - Asn Thr Trp Lys Ser Lys Lys Asn Pro Met Gl - #y Phe Ser Tyr Asp Thr 2625 2630 - # 2635 - # 2640 - - Arg Cys Phe Asp Ser Thr Val Thr Glu Asn As - #p Ile Arg Val Glu Glu 2645 - # 2650 - # 2655 - - Ser Ile Tyr Gln Cys Cys Asp Leu Ala Pro Gl - #u Ala Arg Gln Ala Ile 2660 - # 2665 - # 2670 - - Lys Ser Leu Thr Glu Arg Leu Tyr Ile Gly Gl - #y Pro Leu Thr Asn Ser 2675 - # 2680 - # 2685 - - Lys Gly Gln Asn Cys Gly Tyr Arg Arg Cys Ar - #g Ala Ser Gly Val Leu 2690 - # 2695 - # 2700 - - Thr Thr Ser Cys Gly Asn Thr Leu Thr Cys Ty - #r Leu Lys Ala Ser Ala 2705 2710 - # 2715 - # 2720 - - Ala Cys Arg Ala Ala Lys Leu Gln Asp Cys Th - #r Met Leu Val Asn Gly 2725 - # 2730 - # 2735 - - Asp Asp Leu Val Val Ile Cys Glu Ser Ala Gl - #y Thr Gln Glu Asp Ala 2740 - # 2745 - # 2750 - - Ala Ser Leu Arg Val Phe Thr Glu Ala Met Th - #r Arg Tyr Ser Ala Pro 2755 - # 2760 - # 2765 - - Pro Gly Asp Pro Pro Gln Pro Glu Tyr Asp Le - #u Glu Leu Ile Thr Ser 2770 - # 2775 - # 2780 - - Cys Ser Ser Asn Val Ser Val Ala His Asp Al - #a Ser Gly Lys Arg Val 2785 2790 - # 2795 - # 2800 - - Tyr Tyr Leu Thr Arg Asp Pro Thr Thr Pro Le - #u Ala Arg Ala Ala Trp 2805 - # 2810 - # 2815 - - Glu Thr Ala Arg His Thr Pro Val Asn Ser Tr - #p Leu Gly Asn Ile Ile 2820 - # 2825 - # 2830 - - Met Tyr Ala Pro Thr Leu Trp Ala Arg Met Il - #e Leu Met Thr His Phe 2835 - # 2840 - # 2845 - - Phe Ser Ile Leu Leu Ala Gln Glu Gln Leu Gl - #u Lys Ala Leu Asp Cys 2850 - # 2855 - # 2860 - - Gln Ile Tyr Gly Ala Cys Tyr Ser Ile Glu Pr - #o Leu Asp Leu Pro Gln 2865 2870 - # 2875 - # 2880 - - Ile Ile Glu Arg Leu His Gly Leu Ser Ala Ph - #e Ser Leu His Ser Tyr 2885 - # 2890 - # 2895 - - Ser Pro Gly Glu Ile Asn Arg Val Ala Ser Cy - #s Leu Arg Lys Leu Gly 2900 - # 2905 - # 2910 - - Val Pro Pro Leu Arg Val Trp Arg His Arg Al - #a Arg Ser Val Arg Ala 2915 - # 2920 - # 2925 - - Arg Leu Leu Ser Gln Gly Gly Arg Ala Ala Th - #r Cys Gly Lys Tyr Leu 2930 - # 2935 - # 2940 - - Phe Asn Trp Ala Val Lys Thr Lys Leu Lys Le - #u Thr Pro Ile Pro Ala 2945 2950 - # 2955 - # 2960 - - Ala Ser Arg Leu Asp Leu Ser Gly Trp Phe Va - #l Ala Gly Tyr Ser Gly 2965 - # 2970 - # 2975 - - Gly Asp Ile Tyr His Ser Leu Ser Arg Ala Ar - #g Pro Arg Trp Phe Met 2980 - # 2985 - # 2990 - - Leu Cys Leu Leu Leu Leu Ser Val Gly Val Gl - #y Ile Tyr Leu Leu Pro 2995 - # 3000 - # 3005 - - Asn Arg 3010 - - - - (2) INFORMATION FOR SEQ ID NO:15: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 90 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..90 (D) OTHER INFORMATION: - #/note: "sequence = 474 - 563 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..90 - - (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:15: - - GCG CCC AGG AAG ACT TCC GAG CGG TCG CAA CC - #T CGT GGA AGG CGA CAA 48 Ala Pro Arg Lys Thr Ser Glu Arg Ser Gln Pr - #o Arg Gly Arg Arg Gln 1 5 - # 10 - # 15 - - CCT ATC CCC AAG GCT CGC CGG CCC GAG GGC AG - #G ACC TGG GCT - # 90 Pro Ile Pro Lys Ala Arg Arg Pro Glu Gly Ar - #g Thr Trp Ala 20 - # 25 - # 30 - - - - (2) INFORMATION FOR SEQ ID NO:16: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 30 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16: - - Ala Pro Arg Lys Thr Ser Glu Arg Ser Gln Pr - #o Arg Gly Arg Arg Gln 1 5 - # 10 - # 15 - - Pro Ile Pro Lys Ala Arg Arg Pro Glu Gly Ar - #g Thr Trp Ala 20 - # 25 - # 30 - - - - (2) INFORMATION FOR SEQ ID NO:17: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 228 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..228 (D) OTHER INFORMATION: - #/note: "sequence = 678 - 905 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..228 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17: - - TCG CGT AAT TTG GGT AAG GTC ATC GAT ACC CT - #C ACA TGC GGC TTC GCC 48 Ser Arg Asn Leu Gly Lys Val Ile Asp Thr Le - #u Thr Cys Gly Phe Ala 1 5 - # 10 - # 15 - - GAT CTC ATG GGG TAC ATT CCG CTC GTC GGC GC - #C CCC CTG GGG GGC GCT 96 Asp Leu Met Gly Tyr Ile Pro Leu Val Gly Al - #a Pro Leu Gly Gly Ala 20 - # 25 - # 30 - - GCC AGG GCC CTG GCA CAT GGT GTC CGG GTT CT - #G GAG GAC GGC GTG AAC 144 Ala Arg Ala Leu Ala His Gly Val Arg Val Le - #u Glu Asp Gly Val Asn 35 - # 40 - # 45 - - TAT GCA ACA GGG AAT CTG CCC GGT TGC TCT TT - #T TCT ATC TTC CTC TTG 192 Tyr Ala Thr Gly Asn Leu Pro Gly Cys Ser Ph - #e Ser Ile Phe Leu Leu 50 - # 55 - # 60 - - GCT CTG CTG TCC TGC CTG ACC ACC CCA GCT TC - #C GCT- # 228 Ala Leu Leu Ser Cys Leu Thr Thr Pro Ala Se - #r Ala 65 - # 70 - # 75 - - - - (2) INFORMATION FOR SEQ ID NO:18: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 76 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18: - - Ser Arg Asn Leu Gly Lys Val Ile Asp Thr Le - #u Thr Cys Gly PheAla 1 5 - # 10 - # 15 - - Asp Leu Met Gly Tyr Ile Pro Leu Val Gly Al - #a Pro Leu Gly Gly Ala 20 - # 25 - # 30 - - Ala Arg Ala Leu Ala His Gly Val Arg Val Le - #u Glu Asp Gly Val Asn 35 - # 40 - # 45 - - Tyr Ala Thr Gly Asn Leu Pro Gly Cys Ser Ph - #e Ser Ile Phe Leu Leu 50 - # 55 - # 60 - - Ala Leu Leu Ser Cys Leu Thr Thr Pro Ala Se - #r Ala 65 - # 70 - # 75 - - - - (2) INFORMATION FOR SEQ ID NO:19: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 48 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..48 (D) OTHER INFORMATION: - #/note: "sequence = 906 - 953 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..48 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19: - - TAC GAA GTG CAC AAC GTG TCC GGG ATA TAT CA - #T GTC ACG AAC GAC TGC 48 Tyr Glu Val His Asn Val Ser Gly Ile Tyr Hi - #s Val Thr Asn Asp Cys 1 5 - # 10 - # 15 - - - - (2) INFORMATION FOR SEQ ID NO:20: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 16 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20: - - Tyr Glu Val His Asn Val Ser Gly Ile Tyr Hi - #s Val Thr Asn Asp Cys 1 5 - # 10 - # 15 - - - - (2) INFORMATION FOR SEQ ID NO:21: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 594 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..594 (D) OTHER INFORMATION: - #/note: "sequence = 906 - 1499 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..594 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21: - - TAC GAA GTG CAC AAC GTG TCC GGG ATA TAT CA - #T GTC ACG AAC GAC TGC 48 Tyr Glu Val His Asn Val Ser Gly Ile Tyr Hi - #s Val Thr Asn Asp Cys 1 5 - # 10 - # 15 - - TCC AAC GCA AGC ATT GTG TAT GAG GCA GCG GA - #C TTG ATC ATG CAT ACT 96 Ser Asn Ala Ser Ile Val Tyr Glu Ala Ala As - #p Leu Ile Met His Thr 20 - # 25 - # 30 - - CCT GGG TGC GTG CCC TGC GTT CGG GAA GGC AA - #C TCC TCC CGC TGC TGG 144 Pro Gly Cys Val Pro Cys Val Arg Glu Gly As - #n Ser Ser Arg Cys Trp 35 - # 40 - # 45 - - GTA GCG CTC ACT CCC ACG CTC GCA GCC AGG AA - #C GTC ACC ATC CCC ACC 192 Val Ala Leu Thr Pro Thr Leu Ala Ala Arg As - #n Val Thr Ile Pro Thr 50 - # 55 - # 60 - - ACG ACG ATA CGA CGC CAC GTC GAT CTG CTC GT - #T GGG GCG GCT GCT TTC 240 Thr Thr Ile Arg Arg His Val Asp Leu Leu Va - #l Gly Ala Ala Ala Phe 65 - # 70 - # 75 - # 80 - - TGT TCC GCT ATG TAC GTG GGG GAC CTC TGC GG - #A TCT GTT TTC CTC GTC 288 Cys Ser Ala Met Tyr Val Gly Asp Leu Cys Gl - #y Ser Val Phe Leu Val 85 - # 90 - # 95 - - TCT CAG CTG TTC ACC TTC TCG CCT CGC CGG CA - #T GTG ACA TTA CAG GAC 336 Ser Gln Leu Phe Thr Phe Ser Pro Arg Arg Hi - #s Val Thr Leu Gln Asp 100 - # 105 - # 110 - - TGT AAC TGC TCA ATT TAT CCC GGC CAT GTG TC - #G GGT CAC CGT ATG GCT 384 Cys Asn Cys Ser Ile Tyr Pro Gly His Val Se - #r Gly His Arg Met Ala 115 - # 120 - # 125 - - TGG GAC ATG ATG ATG AAC TGG TCG CCC ACA AC - #A GCC CTA GTG GTG TCG 432 Trp Asp Met Met Met Asn Trp Ser Pro Thr Th - #r Ala Leu Val Val Ser 130 - # 135 - # 140 - - CAG TTA CTC CGG ATC CCA CAA GCC GTC GTG GA - #C ATG GTG GCG GGG GCC 480 Gln Leu Leu Arg Ile Pro Gln Ala Val Val As - #p Met Val Ala Gly Ala 145 1 - #50 1 - #55 1 -#60 - - CAC TGG GGA GTC CTG GCG GGC CTT GCC TAC TA - #T TCC ATG GCG GGGAAC 528 His Trp Gly Val Leu Ala Gly Leu Ala Tyr Ty - #r Ser Met Ala Gly Asn 165 - # 170 - # 175 - - TGG GCT AAG GTT CTG ATT GTG ATG CTA CTT TT - #T GCT GGC GTT GAC GGG 576 Trp Ala Lys Val Leu Ile Val Met Leu Leu Ph - #e Ala Gly Val Asp Gly 180 - # 185 - # 190 - - GAT ACC CAC GTG ACA GGG - # - # - # 594 Asp Thr His Val Thr Gly 195 - - - - (2) INFORMATION FOR SEQ ID NO:22: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 198 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22: - - Tyr Glu Val His Asn Val Ser Gly Ile Tyr Hi - #s Val Thr Asn Asp Cys 1 5 - # 10 - # 15 - - Ser Asn Ala Ser Ile Val Tyr Glu Ala Ala As - #p Leu Ile Met His Thr 20 - # 25 - # 30 - - Pro Gly Cys Val Pro Cys Val Arg Glu Gly As - #n Ser Ser Arg Cys Trp 35 - # 40 - # 45 - - Val Ala Leu Thr Pro Thr Leu Ala Ala Arg As - #n Val Thr Ile Pro Thr 50 - # 55 - # 60 - - Thr Thr Ile Arg Arg His Val Asp Leu Leu Va - #l Gly Ala Ala Ala Phe 65 - # 70 - # 75 - # 80 - - Cys Ser Ala Met Tyr Val Gly Asp Leu Cys Gl - #y Ser Val Phe Leu Val 85 - # 90 - # 95 - - Ser Gln Leu Phe Thr Phe Ser Pro Arg Arg Hi - #s Val Thr Leu Gln Asp 100 - # 105 - # 110 - - Cys Asn Cys Ser Ile Tyr Pro Gly His Val Se - #r Gly His Arg Met Ala 115 - # 120 - # 125 - - Trp Asp Met Met Met Asn Trp Ser Pro Thr Th - #r Ala Leu Val Val Ser 130 - # 135 - # 140 - - Gln Leu Leu Arg Ile Pro Gln Ala Val Val As - #p Met Val Ala Gly Ala 145 1 - #50 1 - #55 1 -#60 - - His Trp Gly Val Leu Ala Gly Leu Ala Tyr Ty - #r Ser Met Ala GlyAsn 165 - # 170 - # 175 - - Trp Ala Lys Val Leu Ile Val Met Leu Leu Ph - #e Ala Gly Val Asp Gly 180 - # 185 - # 190 - - Asp Thr His Val Thr Gly 195 - - - - (2) INFORMATION FOR SEQ ID NO:23: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 27 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..27 (D) OTHER INFORMATION: - #/note: "sequence = 1020 - 1046 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..27 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23: - - GTT CGG GAA GGC AAC TCC TCC CGC TGC - # - # 27 Val Arg Glu Gly Asn Ser Ser Arg Cys 1 5 - - - - (2) INFORMATION FOR SEQ ID NO:24: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: - - Val Arg Glu Gly Asn Ser Ser Arg Cys 1 5 - - - - (2) INFORMATION FOR SEQ ID NO:25: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 102 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..102 (D) OTHER INFORMATION: - #/note: "sequence = 1020 - 1121 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..102 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:25: - - GTT CGG GAA GGC AAC TCC TCC CGC TGC TGG GT - #A GCG CTC ACT CCC ACG 48 Val Arg Glu Gly Asn Ser Ser Arg Cys Trp Va - #l Ala Leu Thr Pro Thr 1 5 - # 10 - # 15 - - CTC GCA GCC AGG AAC GTC ACC ATC CCC ACC AC - #G ACG ATA CGA CGC CAC 96 Leu Ala Ala Arg Asn Val Thr Ile Pro Thr Th - #r Thr Ile Arg Arg His 20 - # 25 - # 30 - - GTC GAT - # - # -# 102 Val Asp - - - - (2) INFORMATION FOR SEQ ID NO:26: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 34 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26: - - Val Arg Glu Gly Asn Ser Ser Arg Cys Trp Va - #l Ala Leu Thr ProThr 1 5 - # 10 - # 15 - - Leu Ala Ala Arg Asn Val Thr Ile Pro Thr Th - #r Thr Ile Arg Arg His 20 - # 25 - # 30 - - Val Asp - - - - (2) INFORMATION FOR SEQ ID NO:27: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 39 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..39 (D) OTHER INFORMATION: - #/note: "sequence = 1194 - 1232 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..39 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27: - - TCT CAG CTG TTC ACC TTC TCG CCT CGC CGG CA - #T GTG ACA - # 39 Ser Gln Leu Phe Thr Phe Ser Pro Arg Arg Hi - #s Val Thr 1 5 - # 10 - - - - (2) INFORMATION FOR SEQ ID NO:28: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 13 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:28: - - Ser Gln Leu Phe Thr Phe Ser Pro Arg Arg Hi - #s Val Thr 1 5 - # 10 - - - - (2) INFORMATION FOR SEQ ID NO:29: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 114 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..114 (D) OTHER INFORMATION: - #/note: "sequence = 1209 - 1322 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..114 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29: - - TTC TCG CCT CGC CGG CAT GTG ACA TTA CAG GA - #C TGT AAC TGC TCA ATT 48 Phe Ser Pro Arg Arg His Val Thr Leu Gln As - #p Cys Asn Cys Ser Ile 1 5 - # 10 - # 15 - - TAT CCC GGC CAT GTG TCG GGT CAC CGT ATG GC - #T TGG GAC ATG ATG ATG 96 Tyr Pro Gly His Val Ser Gly His Arg Met Al - #a Trp Asp Met Met Met 20 - # 25 - # 30 - - AAC TGG TCG CCC ACA ACA - # - # - # 114 Asn Trp Ser Pro Thr Thr 35 - - - - (2) INFORMATION FOR SEQ ID NO:30: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 38 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:30: - - Phe Ser Pro Arg Arg His Val Thr Leu Gln As - #p Cys Asn Cys Ser Ile 1 5 - # 10 - # 15 - - Tyr Pro Gly His Val Ser Gly His Arg Met Al - #a Trp Asp Met Met Met 20 - # 25 - # 30 - - Asn Trp Ser Pro Thr Thr 35 - - - - (2) INFORMATION FOR SEQ ID NO:31: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7917 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..7862 - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..7916 (D) OTHER INFORMATION: - #/note= "sequence = 1500 - 9416 of SEQ ID - #NO: 1" - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:31: - - GGG GCG CAA GCC AAA ACC ACC AAC AGG CTC GT - #G TCC ATG TTC GCA AGT 48 Gly Ala Gln Ala Lys Thr Thr Asn Arg Leu Va - #l Ser Met Phe Ala Ser 1 5 - # 10 - # 15 - - GGG CCG TCT CAG AAA ATC CAG CTT ATA AAC AC - #C AAT GGG AGT TGG CAC 96 Gly Pro Ser Gln Lys Ile Gln Leu Ile Asn Th - #r Asn Gly Ser Trp His 20 - # 25 - # 30 - - ATC AAC AGG ACT GCC CTG AAC TGC AAT GAC TC - #T CTC CAG ACT GGG TTT 144 Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp Se - #r Leu Gln Thr Gly Phe 35 - # 40 - # 45 - - CTT GCC GCG CTG TTC TAC ACA CAT AGT TTC AA - #C TCG TCC GGG TGC CCA 192 Leu Ala Ala Leu Phe Tyr Thr His Ser Phe As - #n Ser Ser Gly Cys Pro 50 - # 55 - # 60 - - GAG CGC ATG GCC CAG TGC CGC ACC ATT GAC AA - #G TTC GAC CAG GGA TGG 240 Glu Arg Met Ala Gln Cys Arg Thr Ile Asp Ly - #s Phe Asp Gln Gly Trp 65 - # 70 - # 75 - # 80 - - GGT CCC ATT ACT TAT GCT GAG TCT AGC AGA TC - #A GAC CAG AGG CCA TAT 288 Gly Pro Ile Thr Tyr Ala Glu Ser Ser Arg Se - #r Asp Gln Arg Pro Tyr 85 - # 90 - # 95 - - TGC TGG CAC TAC CCA CCT CCA CAA TGT ACC AT - #C GTA CCT GCG TCG GAG 336 Cys Trp His Tyr Pro Pro Pro Gln Cys Thr Il - #e Val Pro Ala Ser Glu 100 - # 105 - # 110 - - GTG TGC GGC CCA GTG TAC TGC TTC ACC CCA AG - #C CCT GTC GTC GTG GGG 384 Val Cys Gly Pro Val Tyr Cys Phe Thr Pro Se - #r Pro Val Val Val Gly 115 - # 120 - # 125 - - ACG ACC GAT CGT TTC GGT GTC CCT ACG TAT AG - #A TGG GGG GAG AAC GAG 432 Thr Thr Asp Arg Phe Gly Val Pro Thr Tyr Ar - #g Trp Gly Glu Asn Glu 130 - # 135 - # 140 - - ACT GAC GTG CTG CTG CTC AAC AAC ACG CGG CC - #G CCG CAA GGC AAC TGG 480 Thr Asp Val Leu Leu Leu Asn Asn Thr Arg Pr - #o Pro Gln Gly Asn Trp 145 1 - #50 1 - #55 1 -#60 - - TTC GGC TGC ACA TGG ATG AAT AGC ACC GGG TT - #C ACC AAG ACA TGTGGG 528 Phe Gly Cys Thr Trp Met Asn Ser Thr Gly Ph - #e Thr Lys Thr Cys Gly 165 - # 170 - # 175 - - GGG CCC CCG TGT AAC ATC GGG GGG GTC GGC AA - #C AAC ACC CTG ACC TGC 576 Gly Pro Pro Cys Asn Ile Gly Gly Val Gly As - #n Asn Thr Leu Thr Cys 180 - # 185 - # 190 - - CCC ACG GAC TGC TTC CGG AAG CAC CCC GAG GC - #T ACC TAC ACA AAA TGT 624 Pro Thr Asp Cys Phe Arg Lys His Pro Glu Al - #a Thr Tyr Thr Lys Cys 195 - # 200 - # 205 - - GGT TCG GGG CCT TGG CTG ACA CCT AGG TGC AT - #G GTT GAC TAT CCA TAC 672 Gly Ser Gly Pro Trp Leu Thr Pro Arg Cys Me - #t Val Asp Tyr Pro Tyr 210 - # 215 - # 220 - - AGG CTC TGG CAT TAC CCC TGC ACT GTT AAC TT - #T ACC ATC TTC AAG GTT 720 Arg Leu Trp His Tyr Pro Cys Thr Val Asn Ph - #e Thr Ile Phe Lys Val 225 2 - #30 2 - #35 2 -#40 - - AGG ATG TAT GTG GGG GGG GTG GAG CAC AGG CT - #C AAT GCT GCA TGCAAT 768 Arg Met Tyr Val Gly Gly Val Glu His Arg Le - #u Asn Ala Ala Cys Asn 245 - # 250 - # 255 - - TGG ACC CGA GGA GAG CGT TGT GAC TTG GAG GA - #C AGG GAT AGG CCG GAG 816 Trp Thr Arg Gly Glu Arg Cys Asp Leu Glu As - #p Arg Asp Arg Pro Glu 260 - # 265 - # 270 - - CTC AGC CCG CTG CTG CTG TCT ACA ACA GAG TG - #G CAG GTA CTG CCC TGT 864 Leu Ser Pro Leu Leu Leu Ser Thr Thr Glu Tr - #p Gln Val Leu Pro Cys 275 - # 280 - # 285 - - TCC TTC ACC ACC CTA CCA GCT CTG TCC ACT GG - #C TTG ATT CAC CTC CAT 912 Ser Phe Thr Thr Leu Pro Ala Leu Ser Thr Gl - #y Leu Ile His Leu His 290 - # 295 - # 300 - - CAG AAC ATC GTG GAC GTG CAA TAC CTA TAC GG - #T ATA GGG TCA GCG GTT 960 Gln Asn Ile Val Asp Val Gln Tyr Leu Tyr Gl - #y Ile Gly Ser Ala Val 305 3 - #10 3 - #15 3 -#20 - - GTC TCC TTT GCA ATC AAA TGG GAG TAT GTC CT - #G TTG CTT TTC CTTCTC 1008 Val Ser Phe Ala Ile Lys Trp Glu Tyr Val Le - #u Leu Leu Phe Leu Leu 325 - # 330 - # 335 - - CTA GCG GAC GCA CGT GTC TGT GCC TGC TTG TG - #G ATG ATG CTG CTG ATA 1056 Leu Ala Asp Ala Arg Val Cys Ala Cys Leu Tr - #p Met Met Leu Leu Ile 340 - # 345 - # 350 - - GCC CAG GCC GAG GCC GCC TTG GAG AAC CTG GT - #G GTC CTC AAT TCG GCG 1104 Ala Gln Ala Glu Ala Ala Leu Glu Asn Leu Va - #l Val Leu Asn Ser Ala 355 - # 360 - # 365 - - TCT GTG GCC GGC GCA CAT GGC ATC CTC TCC TT - #C CTT GTG TTC TTC TGT 1152 Ser Val Ala Gly Ala His Gly Ile Leu Ser Ph - #e Leu Val Phe Phe Cys 370 - # 375 - # 380 - - GCC GCC TGG TAC ATC AAA GGC AGG CTG GTC CC - #T GGG GCG ACA TAT GCT 1200 Ala Ala Trp Tyr Ile Lys Gly Arg Leu Val Pr - #o Gly Ala Thr Tyr Ala 385 3 - #90 3 - #95 4 -#00 - - CTT TAT GGC GTG TGG CCG CTG CTC CTG CTC TT - #G CTG GCA TTA CCACCG 1248 Leu Tyr Gly Val Trp Pro Leu Leu Leu Leu Le - #u Leu Ala Leu Pro Pro 405 - # 410 - # 415 - - CGA GCT TAC GCC ATG GAC CGG GAG ATG GCT GC - #A TCG TGC GGA GGC GCG 1296 Arg Ala Tyr Ala Met Asp Arg Glu Met Ala Al - #a Ser Cys Gly Gly Ala 420 - # 425 - # 430 - - GTT TTT GTG GGT CTG GTA CTC CTG ACT TTG TC - #A CCA TAC TAC AAG GTG 1344 Val Phe Val Gly Leu Val Leu Leu Thr Leu Se - #r Pro Tyr Tyr Lys Val 435 - # 440 - # 445 - - TTC CTC GCT AGG CTC ATA TGG TGG TTA CAA TA - #T TTT ACC ACC AGA GCC 1392 Phe Leu Ala Arg Leu Ile Trp Trp Leu Gln Ty - #r Phe Thr Thr Arg Ala 450 - # 455 - # 460 - - GAG GCG GAC TTA CAT GTG TGG ATC CCC CCC CT - #C AAC GCT CGG GGA GGC 1440 Glu Ala Asp Leu His Val Trp Ile Pro Pro Le - #u Asn Ala Arg Gly Gly 465 4 - #70 4 - #75 4 -#80 - - CGC GAT GCC ATC ATC CTC CTC ATG TGC GCA GT - #C CAT CCA GAG CTAATC 1488 Arg Asp Ala Ile Ile Leu Leu Met Cys Ala Va - #l His Pro Glu Leu Ile 485 - # 490 - # 495 - - TTT GAC ATC ACC AAA CTT CTA ATT GCC ATA CT - #C GGT CCG CTC ATG GTG 1536 Phe Asp Ile Thr Lys Leu Leu Ile Ala Ile Le - #u Gly Pro Leu Met Val 500 - # 505 - # 510 - - CTC CAA GCT GGC ATA ACC AGA GTG CCG TAC TT - #C GTG CGC GCT CAA GGG 1584 Leu Gln Ala Gly Ile Thr Arg Val Pro Tyr Ph - #e Val Arg Ala Gln Gly 515 - # 520 - # 525 - - CTC ATT CAT GCA TGC ATG TTA GTG CGG AAG GT - #C GCT GGG GGT CAT TAT 1632 Leu Ile His Ala Cys Met Leu Val Arg Lys Va - #l Ala Gly Gly His Tyr 530 - # 535 - # 540 - - GTC CAA ATG GCC TTC ATG AAG CTG GGC GCG CT - #G ACA GGC ACG TAC ATT 1680 Val Gln Met Ala Phe Met Lys Leu Gly Ala Le - #u Thr Gly Thr Tyr Ile 545 5 - #50 5 - #55 5 -#60 - - TAC AAC CAT CTT ACC CCG CTA CGG GAT TGG CC - #A CGC GCG GGC CTACGA 1728 Tyr Asn His Leu Thr Pro Leu Arg Asp Trp Pr - #o Arg Ala Gly Leu Arg 565 - # 570 - # 575 - - GAC CTT GCG GTG GCA GTG GAG CCC GTC GTC TT - #C TCC GAC ATG GAG ACC 1776 Asp Leu Ala Val Ala Val Glu Pro Val Val Ph - #e Ser Asp Met Glu Thr 580 - # 585 - # 590 - - AAG ATC ATC ACC TGG GGA GCA GAC ACC GCG GC - #G TGT GGG GAC ATC ATC 1824 Lys Ile Ile Thr Trp Gly Ala Asp Thr Ala Al - #a Cys Gly Asp Ile Ile 595 - # 600 - # 605 - - TTG GGT CTG CCC GTC TCC GCC CGA AGG GGA AA - #G GAG ATA CTC CTG GGC 1872 Leu Gly Leu Pro Val Ser Ala Arg Arg Gly Ly - #s Glu Ile Leu Leu Gly 610 - # 615 - # 620 - - CCG GCC GAT AGT CTT GAA GGG CGG GGG TTG CG - #A CTC CTC GCG CCC ATC 1920 Pro Ala Asp Ser Leu Glu Gly Arg Gly Leu Ar - #g Leu Leu Ala Pro Ile 625 6 - #30 6 - #35 6 -#40 - - ACG GCC TAC TCC CAA CAG ACG CGG GGC CTA CT - #T GGT TGC ATC ATCACT 1968 Thr Ala Tyr Ser Gln Gln Thr Arg Gly Leu Le - #u Gly Cys Ile Ile Thr 645 - # 650 - # 655 - - AGC CTT ACA GGC CGG GAC AAG AAC CAG GTC GA - #G GGA GAG GTT CAG GTG 2016 Ser Leu Thr Gly Arg Asp Lys Asn Gln Val Gl - #u Gly Glu Val Gln Val 660 - # 665 - # 670 - - GTT TCC ACC GCA ACA CAA TCC TTC CTG GCG AC - #C TGC GTC AAC GGC GTG 2064 Val Ser Thr Ala Thr Gln Ser Phe Leu Ala Th - #r Cys Val Asn Gly Val 675 - # 680 - # 685 - - TGT TGG ACC GTT TAC CAT GGT GCT GGC TCA AA - #G ACC TTA GCC GCG CCA 2112 Cys Trp Thr Val Tyr His Gly Ala Gly Ser Ly - #s Thr Leu Ala Ala Pro 690 - # 695 - # 700 - - AAG GGG CCA ATC ACC CAG ATG TAC ACT AAT GT - #G GAC CAG GAC CTC GTC 2160 Lys Gly Pro Ile Thr Gln Met Tyr Thr Asn Va - #l Asp Gln Asp Leu Val 705 7 - #10 7 - #15 7 -#20 - - GGC TGG CCC AAG CCC CCC GGG GCG CGT TCC TT - #G ACA CCA TGC ACCTGT 2208 Gly Trp Pro Lys Pro Pro Gly Ala Arg Ser Le - #u Thr Pro Cys Thr Cys 725 - # 730 - # 735 - - GGC AGC TCA GAC CTT TAC TTG GTC ACG AGA CA - #T GCT GAC GTC ATT CCG 2256 Gly Ser Ser Asp Leu Tyr Leu Val Thr Arg Hi - #s Ala Asp Val Ile Pro 740 - # 745 - # 750 - - GTG CGC CGG CGG GGC GAC AGT AGG GGG AGC CT - #G CTC TCC CCC AGG CCT 2304 Val Arg Arg Arg Gly Asp Ser Arg Gly Ser Le - #u Leu Ser Pro Arg Pro 755 - # 760 - # 765 - - GTC TCC TAC TTG AAG GGC TCT TCG GGT GGT CC - #A CTG CTC TGC CCC TTC 2352 Val Ser Tyr Leu Lys Gly Ser Ser Gly Gly Pr - #o Leu Leu Cys Pro Phe 770 - # 775 - # 780 - - GGG CAC GCT GTG GGC ATC TTC CGG GCT GCC GT - #A TGC ACC CGG GGG GTT 2400 Gly His Ala Val Gly Ile Phe Arg Ala Ala Va - #l Cys Thr Arg Gly Val 785 7 - #90 7 - #95 8 -#00 - - GCG AAG GCG GTG GAC TTT GTG CCC GTA GAG TC - #C ATG GAA ACT ACTATG 2448 Ala Lys Ala Val Asp Phe Val Pro Val Glu Se - #r Met Glu Thr Thr Met 805 - # 810 - # 815 - - CGG TCT CCG GTC TTC ACG GAC AAC TCA TCC CC - #C CCG GCC GTA CCG CAG 2496 Arg Ser Pro Val Phe Thr Asp Asn Ser Ser Pr - #o Pro Ala Val Pro Gln 820 - # 825 - # 830 - - TCA TTT CAA GTG GCC CAC CTA CAC GCT CCC AC - #T GGC AGC GGC AAG AGT 2544 Ser Phe Gln Val Ala His Leu His Ala Pro Th - #r Gly Ser Gly Lys Ser 835 - # 840 - # 845 - - ACT AAA GTG CCG GCT GCA TAT GCA GCC CAA GG - #G TAC AAG GTG CTC GTC 2592 Thr Lys Val Pro Ala Ala Tyr Ala Ala Gln Gl - #y Tyr Lys Val Leu Val 850 - # 855 - # 860 - - CTC AAT CCG TCC GTT GCC GCT ACC TTA GGG TT - #T GGG GCG TAT ATG TCT 2640 Leu Asn Pro Ser Val Ala Ala Thr Leu Gly Ph - #e Gly Ala Tyr Met Ser 865 8 - #70 8 - #75 8 -#80 - - AAG GCA CAC GGT ATT GAC CCC AAC ATC AGA AC - #T GGG GTA AGG ACCATT 2688 Lys Ala His Gly Ile Asp Pro Asn Ile Arg Th - #r Gly Val Arg Thr Ile 885 - # 890 - # 895 - - ACC ACA GGC GCC CCC GTC ACA TAC TCT ACC TA - #T GGC AAG TTT CTT GCC 2736 Thr Thr Gly Ala Pro Val Thr Tyr Ser Thr Ty - #r Gly Lys Phe Leu Ala 900 - # 905 - # 910 - - GAT GGT GGT TGC TCT GGG GGC GCT TAT GAC AT - #C ATA ATA TGT GAT GAG 2784 Asp Gly Gly Cys Ser Gly Gly Ala Tyr Asp Il - #e Ile Ile Cys Asp Glu 915 - # 920 - # 925 - - TGC CAT TCA ACT GAC TCG ACT ACA ATC TTG GG - #C ATC GGC ACA GTC CTG 2832 Cys His Ser Thr Asp Ser Thr Thr Ile Leu Gl - #y Ile Gly Thr Val Leu 930 - # 935 - # 940 - - GAC CAA GCG GAG ACG GCT GGA GCG CGG CTT GT - #C GTG CTC GCC ACC GCT 2880 Asp Gln Ala Glu Thr Ala Gly Ala Arg Leu Va - #l Val Leu Ala Thr Ala 945 9 - #50 9 - #55 9 -#60 - - ACG CCT CCG GGA TCG GTC ACC GTG CCA CAC CC - #A AAC ATC GAG GAGGTG 2928 Thr Pro Pro Gly Ser Val Thr Val Pro His Pr - #o Asn Ile Glu Glu Val 965 - # 970 - # 975 - - GCC CTG TCT AAT ACT GGA GAG ATC CCC TTC TA - #T GGC AAA GCC ATC CCC 2976 Ala Leu Ser Asn Thr Gly Glu Ile Pro Phe Ty - #r Gly Lys Ala Ile Pro 980 - # 985 - # 990 - - ATT GAA GCC ATC AGG GGG GGA AGG CAT CTC AT - #T TTC TGT CAT TCC AAG 3024 Ile Glu Ala Ile Arg Gly Gly Arg His Leu Il - #e Phe Cys His Ser Lys 995 - # 1000 - # 1005 - - AAG AAG TGC GAC GAG CTC GCC GCA AAG CTG TC - #A GGC CTC GGA ATC AAC 3072 Lys Lys Cys Asp Glu Leu Ala Ala Lys Leu Se - #r Gly Leu Gly Ile Asn 1010 - # 1015 - # 1020 - - GCT GTG GCG TAT TAC CGG GGG CTC GAT GTG TC - #C GTC ATA CCA ACT ATC 3120 Ala Val Ala Tyr Tyr Arg Gly Leu Asp Val Se - #r Val Ile Pro Thr Ile 1025 1030 - # 1035 - # 1040 - - GGA GAC GTC GTT GTC GTG GCA ACA GAC GCT CT - #G ATG ACG GGC TAT ACG 3168 Gly Asp Val Val Val Val Ala Thr Asp Ala Le - #u Met Thr Gly Tyr Thr 1045 - # 1050 - # 1055 - - GGC GAC TTT GAC TCA GTG ATC GAC TGT AAC AC - #A TGT GTC ACC CAG ACA 3216 Gly Asp Phe Asp Ser Val Ile Asp Cys Asn Th - #r Cys Val Thr Gln Thr 1060 - # 1065 - # 1070 - - GTC GAC TTC AGC TTG GAT CCC ACC TTC ACC AT - #T GAG ACG ACG ACC GTG 3264 Val Asp Phe Ser Leu Asp Pro Thr Phe Thr Il - #e Glu Thr Thr Thr Val 1075 - # 1080 - # 1085 - - CCT CAA GAC GCA GTG TCG CGC TCG CAG CGG CG - #G GGT AGG ACT GGC AGG 3312 Pro Gln Asp Ala Val Ser Arg Ser Gln Arg Ar - #g Gly Arg Thr Gly Arg 1090 - # 1095 - # 1100 - - GGT AGG AGA GGC ATC TAC AGG TTT GTG ACT CC - #G GGA GAA CGG CCC TCG 3360 Gly Arg Arg Gly Ile Tyr Arg Phe Val Thr Pr - #o Gly Glu Arg Pro Ser 1105 1110 - # 1115 - # 1120 - - GGC ATG TTC GAT TCC TCG GTC CTG TGT GAG TG - #C TAT GAC GCG GGC TGT 3408 Gly Met Phe Asp Ser Ser Val Leu Cys Glu Cy - #s Tyr Asp Ala Gly Cys 1125 - # 1130 - # 1135 - - GCT TGG TAC GAG CTC ACC CCG GCC GAG ACC TC - #G GTT AGG TTG CGG GCC 3456 Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Se - #r Val Arg Leu Arg Ala 1140 - # 1145 - # 1150 - - TAC CTG AAC ACA CCA GGG TTG CCC GTT TGC CA - #G GAC CAC CTG GAG TTC 3504 Tyr Leu Asn Thr Pro Gly Leu Pro Val Cys Gl - #n Asp His Leu Glu Phe 1155 - # 1160 - # 1165 - - TGG GAG AGT GTC TTC ACA GGC CTC ACC CAT AT - #A GAT GCA CAC TTC TTG 3552 Trp Glu Ser Val Phe Thr Gly Leu Thr His Il - #e Asp Ala His Phe Leu 1170 - # 1175 - # 1180 - - TCC CAG ACC AAG CAG GCA GGA GAC AAC TTC CC - #C TAC CTG GTA GCA TAC 3600 Ser Gln Thr Lys Gln Ala Gly Asp Asn Phe Pr - #o Tyr Leu Val Ala Tyr 1185 1190 - # 1195 - # 1200 - - CAA GCC ACG GTG TGC GCC AGG GCT CAG GCC CC - #A CCT CCA TCA TGG GAT 3648 Gln Ala Thr Val Cys Ala Arg Ala Gln Ala Pr - #o Pro Pro Ser Trp Asp 1205 - # 1210 - # 1215 - - CAA ATG TGG AAG TGT CTC ATA CGG CTG AAA CC - #T ACG CTG CAC GGG CCA 3696 Gln Met Trp Lys Cys Leu Ile Arg Leu Lys Pr - #o Thr Leu His Gly Pro 1220 - # 1225 - # 1230 - - ACA CCC TTG CTG TAC AGG CTG GGA GCC GTC CA - #G AAT GAG GTC ACC CTC 3744 Thr Pro Leu Leu Tyr Arg Leu Gly Ala Val Gl - #n Asn Glu Val Thr Leu 1235 - # 1240 - # 1245 - - ACC CAC CCC ATA ACC AAA TAC ATC ATG GCA TG - #C ATG TCG GCT GAC CTG 3792 Thr His Pro Ile Thr Lys Tyr Ile Met Ala Cy - #s Met Ser Ala Asp Leu 1250 - # 1255 - # 1260 - - GAG GTC GTC ACT AGC ACC TGG GTG CTG GTG GG - #C GGA GTC CTT GCA GCT 3840 Glu Val Val Thr Ser Thr Trp Val Leu Val Gl - #y Gly Val Leu Ala Ala 1265 1270 - # 1275 - # 1280 - - CTG GCC GCG TAT TGC CTG ACA ACA GGC AGT GT - #G GTC ATT GTG GGT AGG 3888 Leu Ala Ala Tyr Cys Leu Thr Thr Gly Ser Va - #l Val Ile Val Gly Arg 1285 - # 1290 - # 1295 - - ATT ATC TTG TCC GGG AGG CCG GCC ATT GTT CC - #C GAC AGG GAG CTT CTC 3936 Ile Ile Leu Ser Gly Arg Pro Ala Ile Val Pr - #o Asp Arg Glu Leu Leu 1300 - # 1305 - # 1310 - - TAC CAG GAG TTC GAT GAA ATG GAA GAG TGC GC - #C TCG CAC CTC CCT TAC 3984 Tyr Gln Glu Phe Asp Glu Met Glu Glu Cys Al - #a Ser His Leu Pro Tyr 1315 - # 1320 - # 1325 - - ATC GAG CAG GGA ATG CAG CTC GCC GAG CAA TT - #C AAG CAG AAA GCG CTC 4032 Ile Glu Gln Gly Met Gln Leu Ala Glu Gln Ph - #e Lys Gln Lys Ala Leu 1330 - # 1335 - # 1340 - - GGG TTA CTG CAA ACA GCC ACC AAA CAA GCG GA - #G GCT GCT GCT CCC GTG 4080 Gly Leu Leu Gln Thr Ala Thr Lys Gln Ala Gl - #u Ala Ala Ala Pro Val 1345 1350 - # 1355 - # 1360 - - GTG GAG TCC AAG TGG CGA GCC CTT GAG ACA TT - #C TGG GCG AAG CAC ATG 4128 Val Glu Ser Lys Trp Arg Ala Leu Glu Thr Ph - #e Trp Ala Lys His Met 1365 - # 1370 - # 1375 - - TGG AAT TTC ATC AGC GGG ATA CAG TAC TTA GC - #A GGC TTA TCC ACT CTG 4176 Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu Al - #a Gly Leu Ser Thr Leu 1380 - # 1385 - # 1390 - - CCT GGG AAC CCC GCA ATA GCA TCA TTG ATG GC - #A TTC ACA GCC TCT ATC 4224 Pro Gly Asn Pro Ala Ile Ala Ser Leu Met Al - #a Phe Thr Ala Ser Ile 1395 - # 1400 - # 1405 - - ACC AGC CCG CTC ACC ACC CAA AGT ACC CTC CT - #G TTT AAC ATC TTG GGG 4272 Thr Ser Pro Leu Thr Thr Gln Ser Thr Leu Le - #u Phe Asn Ile Leu Gly 1410 - # 1415 - # 1420 - - GGG TGG GTG GCT GCC CAA CTC GCC CCC CCC AG - #C GCC GCT TCG GCT TTC 4320 Gly Trp Val Ala Ala Gln Leu Ala Pro Pro Se - #r Ala Ala Ser Ala Phe 1425 1430 - # 1435 - # 1440 - - GTG GGC GCC GGC ATC GCC GGT GCG GCT GTT GG - #C AGC ATA GGC CTT GGG 4368 Val Gly Ala Gly Ile Ala Gly Ala Ala Val Gl - #y Ser Ile Gly Leu Gly 1445 - # 1450 - # 1455 - - AAG GTG CTT GTG GAC ATT CTG GCG GGT TAT GG - #A GCA GGA GTG GCC GGC 4416 Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gl - #y Ala Gly Val Ala Gly 1460 - # 1465 - # 1470 - - GCG CTC GTG GCC TTT AAG GTC ATG AGC GGC GA - #G ATG CCC TCC ACC GAG 4464 Ala Leu Val Ala Phe Lys Val Met Ser Gly Gl - #u Met Pro Ser Thr Glu 1475 - # 1480 - # 1485 - - GAC CTG GTC AAT CTA CTT CCT GCC ATC CTC TC - #T CCT GGC GCC CTG GTC 4512 Asp Leu Val Asn Leu Leu Pro Ala Ile Leu Se - #r Pro Gly Ala Leu Val 1490 - # 1495 - # 1500 - - GTC GGG GTC GTG TGT GCA GCA ATA CTG CGT CG - #A CAC GTG GGT CCG GGA 4560 Val Gly Val Val Cys Ala Ala Ile Leu Arg Ar - #g His Val Gly Pro Gly 1505 1510 - # 1515 - # 1520 - - GAG GGG GCT GTG CAG TGG ATG AAC CGG CTG AT - #A GCG TTC GCC TCG CGG 4608 Glu Gly Ala Val Gln Trp Met Asn Arg Leu Il - #e Ala Phe Ala Ser Arg 1525 - # 1530 - # 1535 - - GGT AAT CAT GTT TCC CCC ACG CAC TAT GTG CC - #T GAG AGC GAC GCC GCA 4656 Gly Asn His Val Ser Pro Thr His Tyr Val Pr - #o Glu Ser Asp Ala Ala 1540 - # 1545 - # 1550 - - GCG CGT GTT ACT CAG ATC CTC TCC AGC CTT AC - #C ATC ACT CAG CTG CTG 4704 Ala Arg Val Thr Gln Ile Leu Ser Ser Leu Th - #r Ile Thr Gln Leu Leu 1555 - # 1560 - # 1565 - - AAA AGG CTC CAC CAG TGG ATT AAT GAA GAC TG - #C TCC ACA CCG TGT TCC 4752 Lys Arg Leu His Gln Trp Ile Asn Glu Asp Cy - #s Ser Thr Pro Cys Ser 1570 - # 1575 - # 1580 - - GGC TCG TGG CTA AGG GAT GTT TGG GAC TGG AT - #A TGC ACG GTG TTG ACT 4800 Gly Ser Trp Leu Arg Asp Val Trp Asp Trp Il - #e Cys Thr Val Leu Thr 1585 1590 - # 1595 - # 1600 - - GAC TTC AAG ACC TGG CTC CAG TCC AAG CTC CT - #G CCG CAG CTA CCT GGA 4848 Asp Phe Lys Thr Trp Leu Gln Ser Lys Leu Le - #u Pro Gln Leu Pro Gly 1605 - # 1610 - # 1615 - - GTC CCT TTT TTC TCG TGC CAA CGC GGG TAC AA - #G GGA GTC TGG CGG GGA 4896 Val Pro Phe Phe Ser Cys Gln Arg Gly Tyr Ly - #s Gly Val Trp Arg Gly 1620 - # 1625 - # 1630 - - GAC GGC ATC ATG CAA ACC ACC TGC CCA TGT GG - #A GCA CAG ATC ACC GGA 4944 Asp Gly Ile Met Gln Thr Thr Cys Pro Cys Gl - #y Ala Gln Ile Thr Gly 1635 - # 1640 - # 1645 - - CAT GTC AAA AAC GGT TCC ATG AGG ATC GTC GG - #G CCT AAG ACC TGC AGC 4992 His Val Lys Asn Gly Ser Met Arg Ile Val Gl - #y Pro Lys Thr Cys Ser 1650 - # 1655 - # 1660 - - AAC ACG TGG CAT GGA ACA TTC CCC ATC AAC GC - #A TAC ACC ACG GGC CCC 5040 Asn Thr Trp His Gly Thr Phe Pro Ile Asn Al - #a Tyr Thr Thr Gly Pro 1665 1670 - # 1675 - # 1680 - - TGC ACA CCC TCT CCA GCG CCA AAC TAT TCT AG - #G GCG CTG TGG CGG GTG 5088 Cys Thr Pro Ser Pro Ala Pro Asn Tyr Ser Ar - #g Ala Leu Trp Arg Val 1685 - # 1690 - # 1695 - - GCC GCT GAG GAG TAC GTG GAG GTC ACG CGG GT - #G GGG GAT TTC CAC TAC 5136 Ala Ala Glu Glu Tyr Val Glu Val Thr Arg Va - #l Gly Asp Phe His Tyr 1700 - # 1705 - # 1710 - - GTG ACG GGC ATG ACC ACT GAC AAC GTA AAG TG - #C CCA TGC CAG GTT CCG 5184 Val Thr Gly Met Thr Thr Asp Asn Val Lys Cy - #s Pro Cys Gln Val Pro 1715 - # 1720 - # 1725 - - GCT CCT GAA TTC TTC TCG GAG GTG GAC GGA GT - #G CGG TTG CAC AGG TAC 5232 Ala Pro Glu Phe Phe Ser Glu Val Asp Gly Va - #l Arg Leu His Arg Tyr 1730 - # 1735 - # 1740 - - GCT CCG GCG TGC AGG CCT CTC CTA CGG GAG GA - #G GTT ACA TTC CAG GTC 5280 Ala Pro Ala Cys Arg Pro Leu Leu Arg Glu Gl - #u Val Thr Phe Gln Val 1745 1750 - # 1755 - # 1760 - - GGG CTC AAC CAA TAC CTG GTT GGG TCA CAG CT - #A CCA TGC GAG CCC GAA 5328 Gly Leu Asn Gln Tyr Leu Val Gly Ser Gln Le - #u Pro Cys Glu Pro Glu 1765 - # 1770 - # 1775 - - CCG GAT GTA GCA GTG CTC ACT TCC ATG CTC AC - #C GAC CCC TCC CAC ATC 5376 Pro Asp Val Ala Val Leu Thr Ser Met Leu Th - #r Asp Pro Ser His Ile 1780 - # 1785 - # 1790 - - ACA GCA GAA ACG GCT AAG CGT AGG TTG GCC AG - #G GGG TCT CCC CCC TCC 5424 Thr Ala Glu Thr Ala Lys Arg Arg Leu Ala Ar - #g Gly Ser Pro Pro Ser 1795 - # 1800 - # 1805 - - TTG GCC AGC TCT TCA GCT AGC CAG TTG TCT GC - #G CCT TCC TTG AAG GCG 5472 Leu Ala Ser Ser Ser Ala Ser Gln Leu Ser Al - #a Pro Ser Leu Lys Ala 1810 - # 1815 - # 1820 - - ACA TGC ACT ACC CAC CAT GTC TCT CCG GAC GC - #T GAC CTC ATC GAG GCC 5520 Thr Cys Thr Thr His His Val Ser Pro Asp Al - #a Asp Leu Ile Glu Ala 1825 1830 - # 1835 - # 1840 - - AAC CTC CTG TGG CGG CAG GAG ATG GGC GGG AA - #C ATC ACC CGC GTG GAG 5568 Asn Leu Leu Trp Arg Gln Glu Met Gly Gly As - #n Ile Thr Arg Val Glu 1845 - # 1850 - # 1855 - - TCG GAG AAC AAG GTG GTA GTC CTG GAC TCT TT - #C GAC CCG CTT CGA GCG 5616 Ser Glu Asn Lys Val Val Val Leu Asp Ser Ph - #e Asp Pro Leu Arg Ala 1860 - # 1865 - # 1870 - - GAG GAG GAT GAG AGG GAA GTA TCC GTT CCG GC - #G GAG ATC CTG CGG AAA 5664 Glu Glu Asp Glu Arg Glu Val Ser Val Pro Al - #a Glu Ile Leu Arg Lys 1875 - # 1880 - # 1885 - - TCC AAG AAG TTC CCC GCA GCG ATG CCC ATC TG - #G GCG CGC CCG GAT TAC 5712 Ser Lys Lys Phe Pro Ala Ala Met Pro Ile Tr - #p Ala Arg Pro Asp Tyr 1890 - # 1895 - # 1900 - - AAC CCT CCA CTG TTA GAG TCC TGG AAG GAC CC - #G GAC TAC GTC CCT CCG 5760 Asn Pro Pro Leu Leu Glu Ser Trp Lys Asp Pr - #o Asp Tyr Val Pro Pro 1905 1910 - # 1915 - # 1920 - - GTG GTG CAC GGG TGC CCG TTG CCA CCT ATC AA - #G GCC CCT CCA ATA CCA 5808 Val Val His Gly Cys Pro Leu Pro Pro Ile Ly - #s Ala Pro Pro Ile Pro 1925 - # 1930 - # 1935 - - CCT CCA CGG AGA AAG AGG ACG GTT GTC CTA AC - #A GAG TCC TCC GTG TCT 5856 Pro Pro Arg Arg Lys Arg Thr Val Val Leu Th - #r Glu Ser Ser Val Ser 1940 - # 1945 - # 1950 - - TCT GCC TTA GCG GAG CTC GCT ACT AAG ACC TT - #C GGC AGC TCC GAA TCA 5904 Ser Ala Leu Ala Glu Leu Ala Thr Lys Thr Ph - #e Gly Ser Ser Glu Ser 1955 - # 1960 - # 1965 - - TCG GCC GTC GAC AGC GGC ACG GCG ACC GCC CT - #T CCT GAC CAG GCC TCC 5952 Ser Ala Val Asp Ser Gly Thr Ala Thr Ala Le - #u Pro Asp Gln Ala Ser 1970 - # 1975 - # 1980 - - GAC GAC GGT GAC AAA GGA TCC GAC GTT GAG TC - #G TAC TCC TCC ATG CCC 6000 Asp Asp Gly Asp Lys Gly Ser Asp Val Glu Se - #r Tyr Ser Ser Met Pro 1985 1990 - # 1995 - # 2000 - - CCC CTT GAG GGG GAA CCG GGG GAC CCC GAT CT - #C AGT GAC GGG TCT TGG 6048 Pro Leu Glu Gly Glu Pro Gly Asp Pro Asp Le - #u Ser Asp Gly Ser Trp 2005 - # 2010 - # 2015 - - TCT ACC GTG AGC GAG GAA GCT AGT GAG GAT GT - #C GTC TGC TGC TCA ATG 6096 Ser Thr Val Ser Glu Glu Ala Ser Glu Asp Va - #l Val Cys Cys Ser Met 2020 - # 2025 - # 2030 - - TCC TAC ACA TGG ACA GGC GCC TTG ATC ACG CC - #A TGC GCT GCG GAG GAA 6144 Ser Tyr Thr Trp Thr Gly Ala Leu Ile Thr Pr - #o Cys Ala Ala Glu Glu 2035 - # 2040 - # 2045 - - AGC AAG CTG CCC ATC AAC GCG TTG AGC AAC TC - #T TTG CTG CGC CAC CAT 6192 Ser Lys Leu Pro Ile Asn Ala Leu Ser Asn Se - #r Leu Leu Arg His His 2050 - # 2055 - # 2060 - - AAC ATG GTT TAT GCC ACA ACA TCT CGC AGC GC - #A GGC CTG CGG CAG AAG 6240 Asn Met Val Tyr Ala Thr Thr Ser Arg Ser Al - #a Gly Leu Arg Gln Lys 2065 2070 - # 2075 - # 2080 - - AAG GTC ACC TTT GAC AGA CTG CAA GTC CTG GA - #C GAC CAC TAC CGG GAC 6288 Lys Val Thr Phe Asp Arg Leu Gln Val Leu As - #p Asp His Tyr Arg Asp 2085 - # 2090 - # 2095 - - GTG CTC AAG GAG ATG AAG GCG AAG GCG TCC AC - #A GTT AAG GCT AAA CTC 6336 Val Leu Lys Glu Met Lys Ala Lys Ala Ser Th - #r Val Lys Ala Lys Leu 2100 - # 2105 - # 2110 - - CTA TCC GTA GAG GAA GCC TGC AAG CTG ACG CC - #C CCA CAT TCG GCC AAA 6384 Leu Ser Val Glu Glu Ala Cys Lys Leu Thr Pr - #o Pro His Ser Ala Lys 2115 - # 2120 - # 2125 - - TCC AAG TTT GGC TAT GGG GCA AAG GAC GTC CG - #G AAC CTA TCC AGC AAG 6432 Ser Lys Phe Gly Tyr Gly Ala Lys Asp Val Ar - #g Asn Leu Ser Ser Lys 2130 - # 2135 - # 2140 - - GCC GTT AAC CAC ATC CAC TCC GTG TGG AAG GA - #C TTG CTG GAA GAC ACT 6480 Ala Val Asn His Ile His Ser Val Trp Lys As - #p Leu Leu Glu Asp Thr 2145 2150 - # 2155 - # 2160 - - GTG ACA CCA ATT GAC ACC ACC ATC ATG GCA AA - #A AAT GAG GTT TTC TGT 6528 Val Thr Pro Ile Asp Thr Thr Ile Met Ala Ly - #s Asn Glu Val Phe Cys 2165 - # 2170 - # 2175 - - GTC CAA CCA GAG AAA GGA GGC CGT AAG CCA GC - #C CGC CTT ATC GTA TTC 6576 Val Gln Pro Glu Lys Gly Gly Arg Lys Pro Al - #a Arg Leu Ile Val Phe 2180 - # 2185 - # 2190 - - CCA GAT CTG GGA GTC CGT GTA TGC GAG AAG AT - #G GCC CTC TAT GAT GTG 6624 Pro Asp Leu Gly Val Arg Val Cys Glu Lys Me - #t Ala Leu Tyr Asp Val 2195 - # 2200 - # 2205 - - GTC TCC ACC CTT CCT CAG GTC GTG ATG GGC TC - #C TCA TAC GGA TTC CAG 6672 Val Ser Thr Leu Pro Gln Val Val Met Gly Se - #r Ser Tyr Gly Phe Gln 2210 - # 2215 - # 2220 - - TAC TCT CCT GGG CAG CGA GTC GAG TTC CTG GT - #G AAT ACC TGG AAA TCA 6720 Tyr Ser Pro Gly Gln Arg Val Glu Phe Leu Va - #l Asn Thr Trp Lys Ser 2225 2230 - # 2235 - # 2240 - - AAG AAA AAC CCC ATG GGC TTT TCA TAT GAC AC - #T CGC TGT TTC GAC TCA 6768 Lys Lys Asn Pro Met Gly Phe Ser Tyr Asp Th - #r Arg Cys Phe Asp Ser 2245 - # 2250 - # 2255 - - ACG GTC ACC GAG AAC GAC ATC CGT GTT GAG GA - #G TCA ATT TAC CAA TGT 6816 Thr Val Thr Glu Asn Asp Ile Arg Val Glu Gl - #u Ser Ile Tyr Gln Cys 2260 - # 2265 - # 2270 - - TGT GAC TTG GCC CCC GAA GCC AGA CAG GCC AT - #A AAA TCG CTC ACA GAG 6864 Cys Asp Leu Ala Pro Glu Ala Arg Gln Ala Il - #e Lys Ser Leu Thr Glu 2275 - # 2280 - # 2285 - - CGG CTT TAT ATC GGG GGT CCT CTG ACT AAT TC - #A AAA GGG CAG AAC TGC 6912 Arg Leu Tyr Ile Gly Gly Pro Leu Thr Asn Se - #r Lys Gly Gln Asn Cys 2290 - # 2295 - # 2300 - - GGT TAT CGC CGG TGC CGC GCG AGC GGC GTG CT - #G ACG ACT AGC TGC GGT 6960 Gly Tyr Arg Arg Cys Arg Ala Ser Gly Val Le - #u Thr Thr Ser Cys Gly 2305 2310 - # 2315 - # 2320 - - AAC ACC CTC ACA TGT TAC TTG AAG GCC TCT GC - #A GCC TGT CGA GCT GCG 7008 Asn Thr Leu Thr Cys Tyr Leu Lys Ala Ser Al - #a Ala Cys Arg Ala Ala 2325 - # 2330 - # 2335 - - AAG CTC CAG GAC TGC ACG ATG CTC GTG AAC GG - #A GAC GAC CTC GTC GTT 7056 Lys Leu Gln Asp Cys Thr Met Leu Val Asn Gl - #y Asp Asp Leu Val Val 2340 - # 2345 - # 2350 - - ATC TGT GAA AGC GCG GGA ACC CAA GAG GAC GC - #G GCG AGC CTA CGA GTC 7104 Ile Cys Glu Ser Ala Gly Thr Gln Glu Asp Al - #a Ala Ser Leu Arg Val 2355 - # 2360 - # 2365 - - TTC ACG GAG GCT ATG ACT AGG TAC TCC GCC CC - #C CCC GGG GAC CCG CCC 7152 Phe Thr Glu Ala Met Thr Arg Tyr Ser Ala Pr - #o Pro Gly Asp Pro Pro 2370 - # 2375 - # 2380 - - CAA CCA GAA TAC GAC TTG GAG CTG ATA ACA TC - #A TGT TCC TCC AAT GTG 7200 Gln Pro Glu Tyr Asp Leu Glu Leu Ile Thr Se - #r Cys Ser Ser Asn Val 2385 2390 - # 2395 - # 2400 - - TCG GTC GCC CAC GAT GCA TCA GGC AAA AGG GT - #G TAC TAC CTC ACC CGT 7248 Ser Val Ala His Asp Ala Ser Gly Lys Arg Va - #l Tyr Tyr Leu Thr Arg 2405 - # 2410 - # 2415 - - GAT CCC ACC ACC CCC CTA GCA CGG GCT GCG TG - #G GAG ACA GCT AGA CAC 7296 Asp Pro Thr Thr Pro Leu Ala Arg Ala Ala Tr - #p Glu Thr Ala Arg His 2420 - # 2425 - # 2430 - - ACT CCA GTT AAC TCC TGG CTA GGC AAC ATT AT - #T ATG TAT GCG CCC ACT 7344 Thr Pro Val Asn Ser Trp Leu Gly Asn Ile Il - #e Met Tyr Ala Pro Thr 2435 - # 2440 - # 2445 - - TTG TGG GCA AGG ATG ATT CTG ATG ACT CAC TT - #C TTC TCC ATC CTT CTA 7392 Leu Trp Ala Arg Met Ile Leu Met Thr His Ph - #e Phe Ser Ile Leu Leu 2450 - # 2455 - # 2460 - - GCG CAG GAG CAA CTT GAA AAA GCC CTG GAC TG - #C CAG ATC TAC GGG GCC 7440 Ala Gln Glu Gln Leu Glu Lys Ala Leu Asp Cy - #s Gln Ile Tyr Gly Ala 2465 2470 - # 2475 - # 2480 - - TGT TAC TCC ATT GAG CCA CTT GAC CTA CCT CA - #G ATC ATT GAA CGA CTC 7488 Cys Tyr Ser Ile Glu Pro Leu Asp Leu Pro Gl - #n Ile Ile Glu Arg Leu 2485 - # 2490 - # 2495 - - CAT GGC CTT AGC GCA TTT TCA CTC CAT AGT TA - #C TCT CCA GGT GAG ATC 7536 His Gly Leu Ser Ala Phe Ser Leu His Ser Ty - #r Ser Pro Gly Glu Ile 2500 - # 2505 - # 2510 - - AAT AGG GTG GCT TCA TGC CTC AGG AAA CTT GG - #G GTA CCA CCC TTG CGA 7584 Asn Arg Val Ala Ser Cys Leu Arg Lys Leu Gl - #y Val Pro Pro Leu Arg 2515 - # 2520 - # 2525 - - GTC TGG AGA CAT CGG GCC AGG AGC GTC CGC GC - #T AGG CTA CTG TCC CAG 7632 Val Trp Arg His Arg Ala Arg Ser Val Arg Al - #a Arg Leu Leu Ser Gln 2530 - # 2535 - # 2540 - - GGA GGG AGG GCC GCC ACT TGT GGC AAA TAC CT - #C TTC AAC TGG GCA GTA 7680 Gly Gly Arg Ala Ala Thr Cys Gly Lys Tyr Le - #u Phe Asn Trp Ala Val 2545 2550 - # 2555 - # 2560 - - AAA ACC AAA CTT AAA CTC ACT CCA ATC CCG GC - #T GCG TCC CGG CTG GAC 7728 Lys Thr Lys Leu Lys Leu Thr Pro Ile Pro Al - #a Ala Ser Arg Leu Asp 2565 - # 2570 - # 2575 - - TTG TCC GGC TGG TTC GTT GCT GGT TAC AGC GG - #G GGA GAC ATA TAT CAC 7776 Leu Ser Gly Trp Phe Val Ala Gly Tyr Ser Gl - #y Gly Asp Ile Tyr His 2580 - # 2585 - # 2590 - - AGC CTG TCT CGT GCC CGA CCC CGT TGG TTC AT - #G CTG TGC CTA CTC CTA 7824 Ser Leu Ser Arg Ala Arg Pro Arg Trp Phe Me - #t Leu Cys Leu Leu Leu 2595 - # 2600 - # 2605 - - CTT TCT GTA GGG GTA GGC ATC TAC CTG CTC CC - #C AAC CG ATGAACGGGG 7872 Leu Ser Val Gly Val Gly Ile Tyr Leu Leu Pr - #o Asn 2610 - # 2615 - # 262 - - AGATAAACAC TCCAGGCCAA TAGGCCATCC CCCTTTTTTT TTTTT - # 7917 - - - - (2) INFORMATION FOR SEQ ID NO:32: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2620 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:32: - - Gly Ala Gln Ala Lys Thr Thr Asn Arg Leu Va - #l Ser Met Phe Ala Ser 1 5 - # 10 - # 15 - - Gly Pro Ser Gln Lys Ile Gln Leu Ile Asn Th - #r Asn Gly Ser Trp His 20 - # 25 - # 30 - - Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp Se - #r Leu Gln Thr Gly Phe 35 - # 40 - # 45 - - Leu Ala Ala Leu Phe Tyr Thr His Ser Phe As - #n Ser Ser Gly Cys Pro 50 - # 55 - # 60 - - Glu Arg Met Ala Gln Cys Arg Thr Ile Asp Ly - #s Phe Asp Gln Gly Trp 65 - # 70 - # 75 - # 80 - - Gly Pro Ile Thr Tyr Ala Glu Ser Ser Arg Se - #r Asp Gln Arg Pro Tyr 85 - # 90 - # 95 - - Cys Trp His Tyr Pro Pro Pro Gln Cys Thr Il - #e Val Pro Ala Ser Glu 100 - # 105 - # 110 - - Val Cys Gly Pro Val Tyr Cys Phe Thr Pro Se - #r Pro Val Val Val Gly 115 - # 120 - # 125 - - Thr Thr Asp Arg Phe Gly Val Pro Thr Tyr Ar - #g Trp Gly Glu Asn Glu 130 - # 135 - # 140 - - Thr Asp Val Leu Leu Leu Asn Asn Thr Arg Pr - #o Pro Gln Gly Asn Trp 145 1 - #50 1 - #55 1 -#60 - - Phe Gly Cys Thr Trp Met Asn Ser Thr Gly Ph - #e Thr Lys Thr CysGly 165 - # 170 - # 175 - - Gly Pro Pro Cys Asn Ile Gly Gly Val Gly As - #n Asn Thr Leu Thr Cys 180 - # 185 - # 190 - - Pro Thr Asp Cys Phe Arg Lys His Pro Glu Al - #a Thr Tyr Thr Lys Cys 195 - # 200 - # 205 - - Gly Ser Gly Pro Trp Leu Thr Pro Arg Cys Me - #t Val Asp Tyr Pro Tyr 210 - # 215 - # 220 - - Arg Leu Trp His Tyr Pro Cys Thr Val Asn Ph - #e Thr Ile Phe Lys Val 225 2 - #30 2 - #35 2 -#40 - - Arg Met Tyr Val Gly Gly Val Glu His Arg Le - #u Asn Ala Ala CysAsn 245 - # 250 - # 255 - - Trp Thr Arg Gly Glu Arg Cys Asp Leu Glu As - #p Arg Asp Arg Pro Glu 260 - # 265 - # 270 - - Leu Ser Pro Leu Leu Leu Ser Thr Thr Glu Tr - #p Gln Val Leu Pro Cys 275 - # 280 - # 285 - - Ser Phe Thr Thr Leu Pro Ala Leu Ser Thr Gl - #y Leu Ile His Leu His 290 - # 295 - # 300 - - Gln Asn Ile Val Asp Val Gln Tyr Leu Tyr Gl - #y Ile Gly Ser Ala Val 305 3 - #10 3 - #15 3 -#20 - - Val Ser Phe Ala Ile Lys Trp Glu Tyr Val Le - #u Leu Leu Phe LeuLeu 325 - # 330 - # 335 - - Leu Ala Asp Ala Arg Val Cys Ala Cys Leu Tr - #p Met Met Leu Leu Ile 340 - # 345 - # 350 - - Ala Gln Ala Glu Ala Ala Leu Glu Asn Leu Va - #l Val Leu Asn Ser Ala 355 - # 360 - # 365 - - Ser Val Ala Gly Ala His Gly Ile Leu Ser Ph - #e Leu Val Phe Phe Cys 370 - # 375 - # 380 - - Ala Ala Trp Tyr Ile Lys Gly Arg Leu Val Pr - #o Gly Ala Thr Tyr Ala 385 3 - #90 3 - #95 4 -#00 - - Leu Tyr Gly Val Trp Pro Leu Leu Leu Leu Le - #u Leu Ala Leu ProPro 405 - # 410 - # 415 - - Arg Ala Tyr Ala Met Asp Arg Glu Met Ala Al - #a Ser Cys Gly Gly Ala 420 - # 425 - # 430 - - Val Phe Val Gly Leu Val Leu Leu Thr Leu Se - #r Pro Tyr Tyr Lys Val 435 - # 440 - # 445 - - Phe Leu Ala Arg Leu Ile Trp Trp Leu Gln Ty - #r Phe Thr Thr Arg Ala 450 - # 455 - # 460 - - Glu Ala Asp Leu His Val Trp Ile Pro Pro Le - #u Asn Ala Arg Gly Gly 465 4 - #70 4 - #75 4 -#80 - - Arg Asp Ala Ile Ile Leu Leu Met Cys Ala Va - #l His Pro Glu LeuIle 485 - # 490 - # 495 - - Phe Asp Ile Thr Lys Leu Leu Ile Ala Ile Le - #u Gly Pro Leu Met Val 500 - # 505 - # 510 - - Leu Gln Ala Gly Ile Thr Arg Val Pro Tyr Ph - #e Val Arg Ala Gln Gly 515 - # 520 - # 525 - - Leu Ile His Ala Cys Met Leu Val Arg Lys Va - #l Ala Gly Gly His Tyr 530 - # 535 - # 540 - - Val Gln Met Ala Phe Met Lys Leu Gly Ala Le - #u Thr Gly Thr Tyr Ile 545 5 - #50 5 - #55 5 -#60 - - Tyr Asn His Leu Thr Pro Leu Arg Asp Trp Pr - #o Arg Ala Gly LeuArg 565 - # 570 - # 575 - - Asp Leu Ala Val Ala Val Glu Pro Val Val Ph - #e Ser Asp Met Glu Thr 580 - # 585 - # 590 - - Lys Ile Ile Thr Trp Gly Ala Asp Thr Ala Al - #a Cys Gly Asp Ile Ile 595 - # 600 - # 605 - - Leu Gly Leu Pro Val Ser Ala Arg Arg Gly Ly - #s Glu Ile Leu Leu Gly 610 - # 615 - # 620 - - Pro Ala Asp Ser Leu Glu Gly Arg Gly Leu Ar - #g Leu Leu Ala Pro Ile 625 6 - #30 6 - #35 6 -#40 - - Thr Ala Tyr Ser Gln Gln Thr Arg Gly Leu Le - #u Gly Cys Ile IleThr 645 - # 650 - # 655 - - Ser Leu Thr Gly Arg Asp Lys Asn Gln Val Gl - #u Gly Glu Val Gln Val 660 - # 665 - # 670 - - Val Ser Thr Ala Thr Gln Ser Phe Leu Ala Th - #r Cys Val Asn Gly Val 675 - # 680 - # 685 - - Cys Trp Thr Val Tyr His Gly Ala Gly Ser Ly - #s Thr Leu Ala Ala Pro 690 - # 695 - # 700 - - Lys Gly Pro Ile Thr Gln Met Tyr Thr Asn Va - #l Asp Gln Asp Leu Val 705 7 - #10 7 - #15 7 -#20 - - Gly Trp Pro Lys Pro Pro Gly Ala Arg Ser Le - #u Thr Pro Cys ThrCys 725 - # 730 - # 735 - - Gly Ser Ser Asp Leu Tyr Leu Val Thr Arg Hi - #s Ala Asp Val Ile Pro 740 - # 745 - # 750 - - Val Arg Arg Arg Gly Asp Ser Arg Gly Ser Le - #u Leu Ser Pro Arg Pro 755 - # 760 - # 765 - - Val Ser Tyr Leu Lys Gly Ser Ser Gly Gly Pr - #o Leu Leu Cys Pro Phe 770 - # 775 - # 780 - - Gly His Ala Val Gly Ile Phe Arg Ala Ala Va - #l Cys Thr Arg Gly Val 785 7 - #90 7 - #95 8 -#00 - - Ala Lys Ala Val Asp Phe Val Pro Val Glu Se - #r Met Glu Thr ThrMet 805 - # 810 - # 815 - - Arg Ser Pro Val Phe Thr Asp Asn Ser Ser Pr - #o Pro Ala Val Pro Gln 820 - # 825 - # 830 - - Ser Phe Gln Val Ala His Leu His Ala Pro Th - #r Gly Ser Gly Lys Ser 835 - # 840 - # 845 - - Thr Lys Val Pro Ala Ala Tyr Ala Ala Gln Gl - #y Tyr Lys Val Leu Val 850 - # 855 - # 860 - - Leu Asn Pro Ser Val Ala Ala Thr Leu Gly Ph - #e Gly Ala Tyr Met Ser 865 8 - #70 8 - #75 8 -#80 - - Lys Ala His Gly Ile Asp Pro Asn Ile Arg Th - #r Gly Val Arg ThrIle 885 - # 890 - # 895 - - Thr Thr Gly Ala Pro Val Thr Tyr Ser Thr Ty - #r Gly Lys Phe Leu Ala 900 - # 905 - # 910 - - Asp Gly Gly Cys Ser Gly Gly Ala Tyr Asp Il - #e Ile Ile Cys Asp Glu 915 - # 920 - # 925 - - Cys His Ser Thr Asp Ser Thr Thr Ile Leu Gl - #y Ile Gly Thr Val Leu 930 - # 935 - # 940 - - Asp Gln Ala Glu Thr Ala Gly Ala Arg Leu Va - #l Val Leu Ala Thr Ala 945 9 - #50 9 - #55 9 -#60 - - Thr Pro Pro Gly Ser Val Thr Val Pro His Pr - #o Asn Ile Glu GluVal 965 - # 970 - # 975 - - Ala Leu Ser Asn Thr Gly Glu Ile Pro Phe Ty - #r Gly Lys Ala Ile Pro 980 - # 985 - # 990 - - Ile Glu Ala Ile Arg Gly Gly Arg His Leu Il - #e Phe Cys His Ser Lys 995 - # 1000 - # 1005 - - Lys Lys Cys Asp Glu Leu Ala Ala Lys Leu Se - #r Gly Leu Gly Ile Asn 1010 - # 1015 - # 1020 - - Ala Val Ala Tyr Tyr Arg Gly Leu Asp Val Se - #r Val Ile Pro Thr Ile 1025 1030 - # 1035 - # 1040 - - Gly Asp Val Val Val Val Ala Thr Asp Ala Le - #u Met Thr Gly Tyr Thr 1045 - # 1050 - # 1055 - - Gly Asp Phe Asp Ser Val Ile Asp Cys Asn Th - #r Cys Val Thr Gln Thr 1060 - # 1065 - # 1070 - - Val Asp Phe Ser Leu Asp Pro Thr Phe Thr Il - #e Glu Thr Thr Thr Val 1075 - # 1080 - # 1085 - - Pro Gln Asp Ala Val Ser Arg Ser Gln Arg Ar - #g Gly Arg Thr Gly Arg 1090 - # 1095 - # 1100 - - Gly Arg Arg Gly Ile Tyr Arg Phe Val Thr Pr - #o Gly Glu Arg Pro Ser 1105 1110 - # 1115 - # 1120 - - Gly Met Phe Asp Ser Ser Val Leu Cys Glu Cy - #s Tyr Asp Ala Gly Cys 1125 - # 1130 - # 1135 - - Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Se - #r Val Arg Leu Arg Ala 1140 - # 1145 - # 1150 - - Tyr Leu Asn Thr Pro Gly Leu Pro Val Cys Gl - #n Asp His Leu Glu Phe 1155 - # 1160 - # 1165 - - Trp Glu Ser Val Phe Thr Gly Leu Thr His Il - #e Asp Ala His Phe Leu 1170 - # 1175 - # 1180 - - Ser Gln Thr Lys Gln Ala Gly Asp Asn Phe Pr - #o Tyr Leu Val Ala Tyr 1185 1190 - # 1195 - # 1200 - - Gln Ala Thr Val Cys Ala Arg Ala Gln Ala Pr - #o Pro Pro Ser Trp Asp 1205 - # 1210 - # 1215 - - Gln Met Trp Lys Cys Leu Ile Arg Leu Lys Pr - #o Thr Leu His Gly Pro 1220 - # 1225 - # 1230 - - Thr Pro Leu Leu Tyr Arg Leu Gly Ala Val Gl - #n Asn Glu Val Thr Leu 1235 - # 1240 - # 1245 - - Thr His Pro Ile Thr Lys Tyr Ile Met Ala Cy - #s Met Ser Ala Asp Leu 1250 - # 1255 - # 1260 - - Glu Val Val Thr Ser Thr Trp Val Leu Val Gl - #y Gly Val Leu Ala Ala 1265 1270 - # 1275 - # 1280 - - Leu Ala Ala Tyr Cys Leu Thr Thr Gly Ser Va - #l Val Ile Val Gly Arg 1285 - # 1290 - # 1295 - - Ile Ile Leu Ser Gly Arg Pro Ala Ile Val Pr - #o Asp Arg Glu Leu Leu 1300 - # 1305 - # 1310 - - Tyr Gln Glu Phe Asp Glu Met Glu Glu Cys Al - #a Ser His Leu Pro Tyr 1315 - # 1320 - # 1325 - - Ile Glu Gln Gly Met Gln Leu Ala Glu Gln Ph - #e Lys Gln Lys Ala Leu 1330 - # 1335 - # 1340 - - Gly Leu Leu Gln Thr Ala Thr Lys Gln Ala Gl - #u Ala Ala Ala Pro Val 1345 1350 - # 1355 - # 1360 - - Val Glu Ser Lys Trp Arg Ala Leu Glu Thr Ph - #e Trp Ala Lys His Met 1365 - # 1370 - # 1375 - - Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu Al - #a Gly Leu Ser Thr Leu 1380 - # 1385 - # 1390 - - Pro Gly Asn Pro Ala Ile Ala Ser Leu Met Al - #a Phe Thr Ala Ser Ile 1395 - # 1400 - # 1405 - - Thr Ser Pro Leu Thr Thr Gln Ser Thr Leu Le - #u Phe Asn Ile Leu Gly 1410 - # 1415 - # 1420 - - Gly Trp Val Ala Ala Gln Leu Ala Pro Pro Se - #r Ala Ala Ser Ala Phe 1425 1430 - # 1435 - # 1440 - - Val Gly Ala Gly Ile Ala Gly Ala Ala Val Gl - #y Ser Ile Gly Leu Gly 1445 - # 1450 - # 1455 - - Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gl - #y Ala Gly Val Ala Gly 1460 - # 1465 - # 1470 - - Ala Leu Val Ala Phe Lys Val Met Ser Gly Gl - #u Met Pro Ser Thr Glu 1475 - # 1480 - # 1485 - - Asp Leu Val Asn Leu Leu Pro Ala Ile Leu Se - #r Pro Gly Ala Leu Val 1490 - # 1495 - # 1500 - - Val Gly Val Val Cys Ala Ala Ile Leu Arg Ar - #g His Val Gly Pro Gly 1505 1510 - # 1515 - # 1520 - - Glu Gly Ala Val Gln Trp Met Asn Arg Leu Il - #e Ala Phe Ala Ser Arg 1525 - # 1530 - # 1535 - - Gly Asn His Val Ser Pro Thr His Tyr Val Pr - #o Glu Ser Asp Ala Ala 1540 - # 1545 - # 1550 - - Ala Arg Val Thr Gln Ile Leu Ser Ser Leu Th - #r Ile Thr Gln Leu Leu 1555 - # 1560 - # 1565 - - Lys Arg Leu His Gln Trp Ile Asn Glu Asp Cy - #s Ser Thr Pro Cys Ser 1570 - # 1575 - # 1580 - - Gly Ser Trp Leu Arg Asp Val Trp Asp Trp Il - #e Cys Thr Val Leu Thr 1585 1590 - # 1595 - # 1600 - - Asp Phe Lys Thr Trp Leu Gln Ser Lys Leu Le - #u Pro Gln Leu Pro Gly 1605 - # 1610 - # 1615 - - Val Pro Phe Phe Ser Cys Gln Arg Gly Tyr Ly - #s Gly Val Trp Arg Gly 1620 - # 1625 - # 1630 - - Asp Gly Ile Met Gln Thr Thr Cys Pro Cys Gl - #y Ala Gln Ile Thr Gly 1635 - # 1640 - # 1645 - - His Val Lys Asn Gly Ser Met Arg Ile Val Gl - #y Pro Lys Thr Cys Ser 1650 - # 1655 - # 1660 - - Asn Thr Trp His Gly Thr Phe Pro Ile Asn Al - #a Tyr Thr Thr Gly Pro 1665 1670 - # 1675 - # 1680 - - Cys Thr Pro Ser Pro Ala Pro Asn Tyr Ser Ar - #g Ala Leu Trp Arg Val 1685 - # 1690 - # 1695 - - Ala Ala Glu Glu Tyr Val Glu Val Thr Arg Va - #l Gly Asp Phe His Tyr 1700 - # 1705 - # 1710 - - Val Thr Gly Met Thr Thr Asp Asn Val Lys Cy - #s Pro Cys Gln Val Pro 1715 - # 1720 - # 1725 - - Ala Pro Glu Phe Phe Ser Glu Val Asp Gly Va - #l Arg Leu His Arg Tyr 1730 - # 1735 - # 1740 - - Ala Pro Ala Cys Arg Pro Leu Leu Arg Glu Gl - #u Val Thr Phe Gln Val 1745 1750 - # 1755 - # 1760 - - Gly Leu Asn Gln Tyr Leu Val Gly Ser Gln Le - #u Pro Cys Glu Pro Glu 1765 - # 1770 - # 1775 - - Pro Asp Val Ala Val Leu Thr Ser Met Leu Th - #r Asp Pro Ser His Ile 1780 - # 1785 - # 1790 - - Thr Ala Glu Thr Ala Lys Arg Arg Leu Ala Ar - #g Gly Ser Pro Pro Ser 1795 - # 1800 - # 1805 - - Leu Ala Ser Ser Ser Ala Ser Gln Leu Ser Al - #a Pro Ser Leu Lys Ala 1810 - # 1815 - # 1820 - - Thr Cys Thr Thr His His Val Ser Pro Asp Al - #a Asp Leu Ile Glu Ala 1825 1830 - # 1835 - # 1840 - - Asn Leu Leu Trp Arg Gln Glu Met Gly Gly As - #n Ile Thr Arg Val Glu 1845 - # 1850 - # 1855 - - Ser Glu Asn Lys Val Val Val Leu Asp Ser Ph - #e Asp Pro Leu Arg Ala 1860 - # 1865 - # 1870 - - Glu Glu Asp Glu Arg Glu Val Ser Val Pro Al - #a Glu Ile Leu Arg Lys 1875 - # 1880 - # 1885 - - Ser Lys Lys Phe Pro Ala Ala Met Pro Ile Tr - #p Ala Arg Pro Asp Tyr 1890 - # 1895 - # 1900 - - Asn Pro Pro Leu Leu Glu Ser Trp Lys Asp Pr - #o Asp Tyr Val Pro Pro 1905 1910 - # 1915 - # 1920 - - Val Val His Gly Cys Pro Leu Pro Pro Ile Ly - #s Ala Pro Pro Ile Pro 1925 - # 1930 - # 1935 - - Pro Pro Arg Arg Lys Arg Thr Val Val Leu Th - #r Glu Ser Ser Val Ser 1940 - # 1945 - # 1950 - - Ser Ala Leu Ala Glu Leu Ala Thr Lys Thr Ph - #e Gly Ser Ser Glu Ser 1955 - # 1960 - # 1965 - - Ser Ala Val Asp Ser Gly Thr Ala Thr Ala Le - #u Pro Asp Gln Ala Ser 1970 - # 1975 - # 1980 - - Asp Asp Gly Asp Lys Gly Ser Asp Val Glu Se - #r Tyr Ser Ser Met Pro 1985 1990 - # 1995 - # 2000 - - Pro Leu Glu Gly Glu Pro Gly Asp Pro Asp Le - #u Ser Asp Gly Ser Trp 2005 - # 2010 - # 2015 - - Ser Thr Val Ser Glu Glu Ala Ser Glu Asp Va - #l Val Cys Cys Ser Met 2020 - # 2025 - # 2030 - - Ser Tyr Thr Trp Thr Gly Ala Leu Ile Thr Pr - #o Cys Ala Ala Glu Glu 2035 - # 2040 - # 2045 - - Ser Lys Leu Pro Ile Asn Ala Leu Ser Asn Se - #r Leu Leu Arg His His 2050 - # 2055 - # 2060 - - Asn Met Val Tyr Ala Thr Thr Ser Arg Ser Al - #a Gly Leu Arg Gln Lys 2065 2070 - # 2075 - # 2080 - - Lys Val Thr Phe Asp Arg Leu Gln Val Leu As - #p Asp His Tyr Arg Asp 2085 - # 2090 - # 2095 - - Val Leu Lys Glu Met Lys Ala Lys Ala Ser Th - #r Val Lys Ala Lys Leu 2100 - # 2105 - # 2110 - - Leu Ser Val Glu Glu Ala Cys Lys Leu Thr Pr - #o Pro His Ser Ala Lys 2115 - # 2120 - # 2125 - - Ser Lys Phe Gly Tyr Gly Ala Lys Asp Val Ar - #g Asn Leu Ser Ser Lys 2130 - # 2135 - # 2140 - - Ala Val Asn His Ile His Ser Val Trp Lys As - #p Leu Leu Glu Asp Thr 2145 2150 - # 2155 - # 2160 - - Val Thr Pro Ile Asp Thr Thr Ile Met Ala Ly - #s Asn Glu Val Phe Cys 2165 - # 2170 - # 2175 - - Val Gln Pro Glu Lys Gly Gly Arg Lys Pro Al - #a Arg Leu Ile Val Phe 2180 - # 2185 - # 2190 - - Pro Asp Leu Gly Val Arg Val Cys Glu Lys Me - #t Ala Leu Tyr Asp Val 2195 - # 2200 - # 2205 - - Val Ser Thr Leu Pro Gln Val Val Met Gly Se - #r Ser Tyr Gly Phe Gln 2210 - # 2215 - # 2220 - - Tyr Ser Pro Gly Gln Arg Val Glu Phe Leu Va - #l Asn Thr Trp Lys Ser 2225 2230 - # 2235 - # 2240 - - Lys Lys Asn Pro Met Gly Phe Ser Tyr Asp Th - #r Arg Cys Phe Asp Ser 2245 - # 2250 - # 2255 - - Thr Val Thr Glu Asn Asp Ile Arg Val Glu Gl - #u Ser Ile Tyr Gln Cys 2260 - # 2265 - # 2270 - - Cys Asp Leu Ala Pro Glu Ala Arg Gln Ala Il - #e Lys Ser Leu Thr Glu 2275 - # 2280 - # 2285 - - Arg Leu Tyr Ile Gly Gly Pro Leu Thr Asn Se - #r Lys Gly Gln Asn Cys 2290 - # 2295 - # 2300 - - Gly Tyr Arg Arg Cys Arg Ala Ser Gly Val Le - #u Thr Thr Ser Cys Gly 2305 2310 - # 2315 - # 2320 - - Asn Thr Leu Thr Cys Tyr Leu Lys Ala Ser Al - #a Ala Cys Arg Ala Ala 2325 - # 2330 - # 2335 - - Lys Leu Gln Asp Cys Thr Met Leu Val Asn Gl - #y Asp Asp Leu Val Val 2340 - # 2345 - # 2350 - - Ile Cys Glu Ser Ala Gly Thr Gln Glu Asp Al - #a Ala Ser Leu Arg Val 2355 - # 2360 - # 2365 - - Phe Thr Glu Ala Met Thr Arg Tyr Ser Ala Pr - #o Pro Gly Asp Pro Pro 2370 - # 2375 - # 2380 - - Gln Pro Glu Tyr Asp Leu Glu Leu Ile Thr Se - #r Cys Ser Ser Asn Val 2385 2390 - # 2395 - # 2400 - - Ser Val Ala His Asp Ala Ser Gly Lys Arg Va - #l Tyr Tyr Leu Thr Arg 2405 - # 2410 - # 2415 - - Asp Pro Thr Thr Pro Leu Ala Arg Ala Ala Tr - #p Glu Thr Ala Arg His 2420 - # 2425 - # 2430 - - Thr Pro Val Asn Ser Trp Leu Gly Asn Ile Il - #e Met Tyr Ala Pro Thr 2435 - # 2440 - # 2445 - - Leu Trp Ala Arg Met Ile Leu Met Thr His Ph - #e Phe Ser Ile Leu Leu 2450 - # 2455 - # 2460 - - Ala Gln Glu Gln Leu Glu Lys Ala Leu Asp Cy - #s Gln Ile Tyr Gly Ala 2465 2470 - # 2475 - # 2480 - - Cys Tyr Ser Ile Glu Pro Leu Asp Leu Pro Gl - #n Ile Ile Glu Arg Leu 2485 - # 2490 - # 2495 - - His Gly Leu Ser Ala Phe Ser Leu His Ser Ty - #r Ser Pro Gly Glu Ile 2500 - # 2505 - # 2510 - - Asn Arg Val Ala Ser Cys Leu Arg Lys Leu Gl - #y Val Pro Pro Leu Arg 2515 - # 2520 - # 2525 - - Val Trp Arg His Arg Ala Arg Ser Val Arg Al - #a Arg Leu Leu Ser Gln 2530 - # 2535 - # 2540 - - Gly Gly Arg Ala Ala Thr Cys Gly Lys Tyr Le - #u Phe Asn Trp Ala Val 2545 2550 - # 2555 - # 2560 - - Lys Thr Lys Leu Lys Leu Thr Pro Ile Pro Al - #a Ala Ser Arg Leu Asp 2565 - # 2570 - # 2575 - - Leu Ser Gly Trp Phe Val Ala Gly Tyr Ser Gl - #y Gly Asp Ile Tyr His 2580 - # 2585 - # 2590 - - Ser Leu Ser Arg Ala Arg Pro Arg Trp Phe Me - #t Leu Cys Leu Leu Leu 2595 - # 2600 - # 2605 - - Leu Ser Val Gly Val Gly Ile Tyr Leu Leu Pr - #o Asn 2610 - # 2615 - # 2620 - - - - (2) INFORMATION FOR SEQ ID NO:33: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1020 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..1020 (D) OTHER INFORMATION: - #/note: "sequence = 1500 - 2519 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..1020 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33: - - GGG GCG CAA GCC AAA ACC ACC AAC AGG CTC GT - #G TCC ATG TTC GCA AGT 48 Gly Ala Gln Ala Lys Thr Thr Asn Arg Leu Va - #l Ser Met Phe Ala Ser 1 5 - # 10 - # 15 - - GGG CCG TCT CAG AAA ATC CAG CTT ATA AAC AC - #C AAT GGG AGT TGG CAC 96 Gly Pro Ser Gln Lys Ile Gln Leu Ile Asn Th - #r Asn Gly Ser Trp His 20 - # 25 - # 30 - - ATC AAC AGG ACT GCC CTG AAC TGC AAT GAC TC - #T CTC CAG ACT GGG TTT 144 Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp Se - #r Leu Gln Thr Gly Phe 35 - # 40 - # 45 - - CTT GCC GCG CTG TTC TAC ACA CAT AGT TTC AA - #C TCG TCC GGG TGC CCA 192 Leu Ala Ala Leu Phe Tyr Thr His Ser Phe As - #n Ser Ser Gly Cys Pro 50 - # 55 - # 60 - - GAG CGC ATG GCC CAG TGC CGC ACC ATT GAC AA - #G TTC GAC CAG GGA TGG 240 Glu Arg Met Ala Gln Cys Arg Thr Ile Asp Ly - #s Phe Asp Gln Gly Trp 65 - # 70 - # 75 - # 80 - - GGT CCC ATT ACT TAT GCT GAG TCT AGC AGA TC - #A GAC CAG AGG CCA TAT 288 Gly Pro Ile Thr Tyr Ala Glu Ser Ser Arg Se - #r Asp Gln Arg Pro Tyr 85 - # 90 - # 95 - - TGC TGG CAC TAC CCA CCT CCA CAA TGT ACC AT - #C GTA CCT GCG TCG GAG 336 Cys Trp His Tyr Pro Pro Pro Gln Cys Thr Il - #e Val Pro Ala Ser Glu 100 - # 105 - # 110 - - GTG TGC GGC CCA GTG TAC TGC TTC ACC CCA AG - #C CCT GTC GTC GTG GGG 384 Val Cys Gly Pro Val Tyr Cys Phe Thr Pro Se - #r Pro Val Val Val Gly 115 - # 120 - # 125 - - ACG ACC GAT CGT TTC GGT GTC CCT ACG TAT AG - #A TGG GGG GAG AAC GAG 432 Thr Thr Asp Arg Phe Gly Val Pro Thr Tyr Ar - #g Trp Gly Glu Asn Glu 130 - # 135 - # 140 - - ACT GAC GTG CTG CTG CTC AAC AAC ACG CGG CC - #G CCG CAA GGC AAC TGG 480 Thr Asp Val Leu Leu Leu Asn Asn Thr Arg Pr - #o Pro Gln Gly Asn Trp 145 1 - #50 1 - #55 1 -#60 - - TTC GGC TGC ACA TGG ATG AAT AGC ACC GGG TT - #C ACC AAG ACA TGTGGG 528 Phe Gly Cys Thr Trp Met Asn Ser Thr Gly Ph - #e Thr Lys Thr Cys Gly 165 - # 170 - # 175 - - GGG CCC CCG TGT AAC ATC GGG GGG GTC GGC AA - #C AAC ACC CTG ACC TGC 576 Gly Pro Pro Cys Asn Ile Gly Gly Val Gly As - #n Asn Thr Leu Thr Cys 180 - # 185 - # 190 - - CCC ACG GAC TGC TTC CGG AAG CAC CCC GAG GC - #T ACC TAC ACA AAA TGT 624 Pro Thr Asp Cys Phe Arg Lys His Pro Glu Al - #a Thr Tyr Thr Lys Cys 195 - # 200 - # 205 - - GGT TCG GGG CCT TGG CTG ACA CCT AGG TGC AT - #G GTT GAC TAT CCA TAC 672 Gly Ser Gly Pro Trp Leu Thr Pro Arg Cys Me - #t Val Asp Tyr Pro Tyr 210 - # 215 - # 220 - - AGG CTC TGG CAT TAC CCC TGC ACT GTT AAC TT - #T ACC ATC TTC AAG GTT 720 Arg Leu Trp His Tyr Pro Cys Thr Val Asn Ph - #e Thr Ile Phe Lys Val 225 2 - #30 2 - #35 2 -#40 - - AGG ATG TAT GTG GGG GGG GTG GAG CAC AGG CT - #C AAT GCT GCA TGCAAT 768 Arg Met Tyr Val Gly Gly Val Glu His Arg Le - #u Asn Ala Ala Cys Asn 245 - # 250 - # 255 - - TGG ACC CGA GGA GAG CGT TGT GAC TTG GAG GA - #C AGG GAT AGG CCG GAG 816 Trp Thr Arg Gly Glu Arg Cys Asp Leu Glu As - #p Arg Asp Arg Pro Glu 260 - # 265 - # 270 - - CTC AGC CCG CTG CTG CTG TCT ACA ACA GAG TG - #G CAG GTA CTG CCC TGT 864 Leu Ser Pro Leu Leu Leu Ser Thr Thr Glu Tr - #p Gln Val Leu Pro Cys 275 - # 280 - # 285 - - TCC TTC ACC ACC CTA CCA GCT CTG TCC ACT GG - #C TTG ATT CAC CTC CAT 912 Ser Phe Thr Thr Leu Pro Ala Leu Ser Thr Gl - #y Leu Ile His Leu His 290 - # 295 - # 300 - - CAG AAC ATC GTG GAC GTG CAA TAC CTA TAC GG - #T ATA GGG TCA GCG GTT 960 Gln Asn Ile Val Asp Val Gln Tyr Leu Tyr Gl - #y Ile Gly Ser Ala Val 305 3 - #10 3 - #15 3 -#20 - - GTC TCC TTT GCA ATC AAA TGG GAG TAT GTC CT - #G TTG CTT TTC CTTCTC 1008 Val Ser Phe Ala Ile Lys Trp Glu Tyr Val Le - #u Leu Leu Phe Leu Leu 325 - # 330 - # 335 - - CTA GCG GAC GCA - # - # - # 1020 Leu Ala Asp Ala 340 - - - - (2) INFORMATION FOR SEQ ID NO:34: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 340 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34: - - Gly Ala Gln Ala Lys Thr Thr Asn Arg Leu Va - #l Ser Met Phe Ala Ser 1 5 - # 10 - # 15 - - Gly Pro Ser Gln Lys Ile Gln Leu Ile Asn Th - #r Asn Gly Ser Trp His 20 - # 25 - # 30 - - Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp Se - #r Leu Gln Thr Gly Phe 35 - # 40 - # 45 - - Leu Ala Ala Leu Phe Tyr Thr His Ser Phe As - #n Ser Ser Gly Cys Pro 50 - # 55 - # 60 - - Glu Arg Met Ala Gln Cys Arg Thr Ile Asp Ly - #s Phe Asp Gln Gly Trp 65 - # 70 - # 75 - # 80 - - Gly Pro Ile Thr Tyr Ala Glu Ser Ser Arg Se - #r Asp Gln Arg Pro Tyr 85 - # 90 - # 95 - - Cys Trp His Tyr Pro Pro Pro Gln Cys Thr Il - #e Val Pro Ala Ser Glu 100 - # 105 - # 110 - - Val Cys Gly Pro Val Tyr Cys Phe Thr Pro Se - #r Pro Val Val Val Gly 115 - # 120 - # 125 - - Thr Thr Asp Arg Phe Gly Val Pro Thr Tyr Ar - #g Trp Gly Glu Asn Glu 130 - # 135 - # 140 - - Thr Asp Val Leu Leu Leu Asn Asn Thr Arg Pr - #o Pro Gln Gly Asn Trp 145 1 - #50 1 - #55 1 -#60 - - Phe Gly Cys Thr Trp Met Asn Ser Thr Gly Ph - #e Thr Lys Thr CysGly 165 - # 170 - # 175 - - Gly Pro Pro Cys Asn Ile Gly Gly Val Gly As - #n Asn Thr Leu Thr Cys 180 - # 185 - # 190 - - Pro Thr Asp Cys Phe Arg Lys His Pro Glu Al - #a Thr Tyr Thr Lys Cys 195 - # 200 - # 205 - - Gly Ser Gly Pro Trp Leu Thr Pro Arg Cys Me - #t Val Asp Tyr Pro Tyr 210 - # 215 - # 220 - - Arg Leu Trp His Tyr Pro Cys Thr Val Asn Ph - #e Thr Ile Phe Lys Val 225 2 - #30 2 - #35 2 -#40 - - Arg Met Tyr Val Gly Gly Val Glu His Arg Le - #u Asn Ala Ala CysAsn 245 - # 250 - # 255 - - Trp Thr Arg Gly Glu Arg Cys Asp Leu Glu As - #p Arg Asp Arg Pro Glu 260 - # 265 - # 270 - - Leu Ser Pro Leu Leu Leu Ser Thr Thr Glu Tr - #p Gln Val Leu Pro Cys 275 - # 280 - # 285 - - Ser Phe Thr Thr Leu Pro Ala Leu Ser Thr Gl - #y Leu Ile His Leu His 290 - # 295 - # 300 - - Gln Asn Ile Val Asp Val Gln Tyr Leu Tyr Gl - #y Ile Gly Ser Ala Val 305 3 - #10 3 - #15 3 -#20 - - Val Ser Phe Ala Ile Lys Trp Glu Tyr Val Le - #u Leu Leu Phe LeuLeu 325 - # 330 - # 335 - - Leu Ala Asp Ala 340 - - - - (2) INFORMATION FOR SEQ ID NO:35: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7863 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..7863 - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..7863 (D) OTHER INFORMATION: - #/note= "sequence = 1500 - 9362 of SEQ ID - #NO: 1" - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:35: - - GGG GCG CAA GCC AAA ACC ACC AAC AGG CTC GT - #G TCC ATG TTC GCA AGT 48 Gly Ala Gln Ala Lys Thr Thr Asn Arg Leu Va - #l Ser Met Phe Ala Ser 1 5 - # 10 - # 15 - - GGG CCG TCT CAG AAA ATC CAG CTT ATA AAC AC - #C AAT GGG AGT TGG CAC 96 Gly Pro Ser Gln Lys Ile Gln Leu Ile Asn Th - #r Asn Gly Ser Trp His 20 - # 25 - # 30 - - ATC AAC AGG ACT GCC CTG AAC TGC AAT GAC TC - #T CTC CAG ACT GGG TTT 144 Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp Se - #r Leu Gln Thr Gly Phe 35 - # 40 - # 45 - - CTT GCC GCG CTG TTC TAC ACA CAT AGT TTC AA - #C TCG TCC GGG TGC CCA 192 Leu Ala Ala Leu Phe Tyr Thr His Ser Phe As - #n Ser Ser Gly Cys Pro 50 - # 55 - # 60 - - GAG CGC ATG GCC CAG TGC CGC ACC ATT GAC AA - #G TTC GAC CAG GGA TGG 240 Glu Arg Met Ala Gln Cys Arg Thr Ile Asp Ly - #s Phe Asp Gln Gly Trp 65 - # 70 - # 75 - # 80 - - GGT CCC ATT ACT TAT GCT GAG TCT AGC AGA TC - #A GAC CAG AGG CCA TAT 288 Gly Pro Ile Thr Tyr Ala Glu Ser Ser Arg Se - #r Asp Gln Arg Pro Tyr 85 - # 90 - # 95 - - TGC TGG CAC TAC CCA CCT CCA CAA TGT ACC AT - #C GTA CCT GCG TCG GAG 336 Cys Trp His Tyr Pro Pro Pro Gln Cys Thr Il - #e Val Pro Ala Ser Glu 100 - # 105 - # 110 - - GTG TGC GGC CCA GTG TAC TGC TTC ACC CCA AG - #C CCT GTC GTC GTG GGG 384 Val Cys Gly Pro Val Tyr Cys Phe Thr Pro Se - #r Pro Val Val Val Gly 115 - # 120 - # 125 - - ACG ACC GAT CGT TTC GGT GTC CCT ACG TAT AG - #A TGG GGG GAG AAC GAG 432 Thr Thr Asp Arg Phe Gly Val Pro Thr Tyr Ar - #g Trp Gly Glu Asn Glu 130 - # 135 - # 140 - - ACT GAC GTG CTG CTG CTC AAC AAC ACG CGG CC - #G CCG CAA GGC AAC TGG 480 Thr Asp Val Leu Leu Leu Asn Asn Thr Arg Pr - #o Pro Gln Gly Asn Trp 145 1 - #50 1 - #55 1 -#60 - - TTC GGC TGC ACA TGG ATG AAT AGC ACC GGG TT - #C ACC AAG ACA TGTGGG 528 Phe Gly Cys Thr Trp Met Asn Ser Thr Gly Ph - #e Thr Lys Thr Cys Gly 165 - # 170 - # 175 - - GGG CCC CCG TGT AAC ATC GGG GGG GTC GGC AA - #C AAC ACC CTG ACC TGC 576 Gly Pro Pro Cys Asn Ile Gly Gly Val Gly As - #n Asn Thr Leu Thr Cys 180 - # 185 - # 190 - - CCC ACG GAC TGC TTC CGG AAG CAC CCC GAG GC - #T ACC TAC ACA AAA TGT 624 Pro Thr Asp Cys Phe Arg Lys His Pro Glu Al - #a Thr Tyr Thr Lys Cys 195 - # 200 - # 205 - - GGT TCG GGG CCT TGG CTG ACA CCT AGG TGC AT - #G GTT GAC TAT CCA TAC 672 Gly Ser Gly Pro Trp Leu Thr Pro Arg Cys Me - #t Val Asp Tyr Pro Tyr 210 - # 215 - # 220 - - AGG CTC TGG CAT TAC CCC TGC ACT GTT AAC TT - #T ACC ATC TTC AAG GTT 720 Arg Leu Trp His Tyr Pro Cys Thr Val Asn Ph - #e Thr Ile Phe Lys Val 225 2 - #30 2 - #35 2 -#40 - - AGG ATG TAT GTG GGG GGG GTG GAG CAC AGG CT - #C AAT GCT GCA TGCAAT 768 Arg Met Tyr Val Gly Gly Val Glu His Arg Le - #u Asn Ala Ala Cys Asn 245 - # 250 - # 255 - - TGG ACC CGA GGA GAG CGT TGT GAC TTG GAG GA - #C AGG GAT AGG CCG GAG 816 Trp Thr Arg Gly Glu Arg Cys Asp Leu Glu As - #p Arg Asp Arg Pro Glu 260 - # 265 - # 270 - - CTC AGC CCG CTG CTG CTG TCT ACA ACA GAG TG - #G CAG GTA CTG CCC TGT 864 Leu Ser Pro Leu Leu Leu Ser Thr Thr Glu Tr - #p Gln Val Leu Pro Cys 275 - # 280 - # 285 - - TCC TTC ACC ACC CTA CCA GCT CTG TCC ACT GG - #C TTG ATT CAC CTC CAT 912 Ser Phe Thr Thr Leu Pro Ala Leu Ser Thr Gl - #y Leu Ile His Leu His 290 - # 295 - # 300 - - CAG AAC ATC GTG GAC GTG CAA TAC CTA TAC GG - #T ATA GGG TCA GCG GTT 960 Gln Asn Ile Val Asp Val Gln Tyr Leu Tyr Gl - #y Ile Gly Ser Ala Val 305 3 - #10 3 - #15 3 -#20 - - GTC TCC TTT GCA ATC AAA TGG GAG TAT GTC CT - #G TTG CTT TTC CTTCTC 1008 Val Ser Phe Ala Ile Lys Trp Glu Tyr Val Le - #u Leu Leu Phe Leu Leu 325 - # 330 - # 335 - - CTA GCG GAC GCA CGT GTC TGT GCC TGC TTG TG - #G ATG ATG CTG CTG ATA 1056 Leu Ala Asp Ala Arg Val Cys Ala Cys Leu Tr - #p Met Met Leu Leu Ile 340 - # 345 - # 350 - - GCC CAG GCC GAG GCC GCC TTG GAG AAC CTG GT - #G GTC CTC AAT TCG GCG 1104 Ala Gln Ala Glu Ala Ala Leu Glu Asn Leu Va - #l Val Leu Asn Ser Ala 355 - # 360 - # 365 - - TCT GTG GCC GGC GCA CAT GGC ATC CTC TCC TT - #C CTT GTG TTC TTC TGT 1152 Ser Val Ala Gly Ala His Gly Ile Leu Ser Ph - #e Leu Val Phe Phe Cys 370 - # 375 - # 380 - - GCC GCC TGG TAC ATC AAA GGC AGG CTG GTC CC - #T GGG GCG ACA TAT GCT 1200 Ala Ala Trp Tyr Ile Lys Gly Arg Leu Val Pr - #o Gly Ala Thr Tyr Ala 385 3 - #90 3 - #95 4 -#00 - - CTT TAT GGC GTG TGG CCG CTG CTC CTG CTC TT - #G CTG GCA TTA CCACCG 1248 Leu Tyr Gly Val Trp Pro Leu Leu Leu Leu Le - #u Leu Ala Leu Pro Pro 405 - # 410 - # 415 - - CGA GCT TAC GCC ATG GAC CGG GAG ATG GCT GC - #A TCG TGC GGA GGC GCG 1296 Arg Ala Tyr Ala Met Asp Arg Glu Met Ala Al - #a Ser Cys Gly Gly Ala 420 - # 425 - # 430 - - GTT TTT GTG GGT CTG GTA CTC CTG ACT TTG TC - #A CCA TAC TAC AAG GTG 1344 Val Phe Val Gly Leu Val Leu Leu Thr Leu Se - #r Pro Tyr Tyr Lys Val 435 - # 440 - # 445 - - TTC CTC GCT AGG CTC ATA TGG TGG TTA CAA TA - #T TTT ACC ACC AGA GCC 1392 Phe Leu Ala Arg Leu Ile Trp Trp Leu Gln Ty - #r Phe Thr Thr Arg Ala 450 - # 455 - # 460 - - GAG GCG GAC TTA CAT GTG TGG ATC CCC CCC CT - #C AAC GCT CGG GGA GGC 1440 Glu Ala Asp Leu His Val Trp Ile Pro Pro Le - #u Asn Ala Arg Gly Gly 465 4 - #70 4 - #75 4 -#80 - - CGC GAT GCC ATC ATC CTC CTC ATG TGC GCA GT - #C CAT CCA GAG CTAATC 1488 Arg Asp Ala Ile Ile Leu Leu Met Cys Ala Va - #l His Pro Glu Leu Ile 485 - # 490 - # 495 - - TTT GAC ATC ACC AAA CTT CTA ATT GCC ATA CT - #C GGT CCG CTC ATG GTG 1536 Phe Asp Ile Thr Lys Leu Leu Ile Ala Ile Le - #u Gly Pro Leu Met Val 500 - # 505 - # 510 - - CTC CAA GCT GGC ATA ACC AGA GTG CCG TAC TT - #C GTG CGC GCT CAA GGG 1584 Leu Gln Ala Gly Ile Thr Arg Val Pro Tyr Ph - #e Val Arg Ala Gln Gly 515 - # 520 - # 525 - - CTC ATT CAT GCA TGC ATG TTA GTG CGG AAG GT - #C GCT GGG GGT CAT TAT 1632 Leu Ile His Ala Cys Met Leu Val Arg Lys Va - #l Ala Gly Gly His Tyr 530 - # 535 - # 540 - - GTC CAA ATG GCC TTC ATG AAG CTG GGC GCG CT - #G ACA GGC ACG TAC ATT 1680 Val Gln Met Ala Phe Met Lys Leu Gly Ala Le - #u Thr Gly Thr Tyr Ile 545 5 - #50 5 - #55 5 -#60 - - TAC AAC CAT CTT ACC CCG CTA CGG GAT TGG CC - #A CGC GCG GGC CTACGA 1728 Tyr Asn His Leu Thr Pro Leu Arg Asp Trp Pr - #o Arg Ala Gly Leu Arg 565 - # 570 - # 575 - - GAC CTT GCG GTG GCA GTG GAG CCC GTC GTC TT - #C TCC GAC ATG GAG ACC 1776 Asp Leu Ala Val Ala Val Glu Pro Val Val Ph - #e Ser Asp Met Glu Thr 580 - # 585 - # 590 - - AAG ATC ATC ACC TGG GGA GCA GAC ACC GCG GC - #G TGT GGG GAC ATC ATC 1824 Lys Ile Ile Thr Trp Gly Ala Asp Thr Ala Al - #a Cys Gly Asp Ile Ile 595 - # 600 - # 605 - - TTG GGT CTG CCC GTC TCC GCC CGA AGG GGA AA - #G GAG ATA CTC CTG GGC 1872 Leu Gly Leu Pro Val Ser Ala Arg Arg Gly Ly - #s Glu Ile Leu Leu Gly 610 - # 615 - # 620 - - CCG GCC GAT AGT CTT GAA GGG CGG GGG TTG CG - #A CTC CTC GCG CCC ATC 1920 Pro Ala Asp Ser Leu Glu Gly Arg Gly Leu Ar - #g Leu Leu Ala Pro Ile 625 6 - #30 6 - #35 6 -#40 - - ACG GCC TAC TCC CAA CAG ACG CGG GGC CTA CT - #T GGT TGC ATC ATCACT 1968 Thr Ala Tyr Ser Gln Gln Thr Arg Gly Leu Le - #u Gly Cys Ile Ile Thr 645 - # 650 - # 655 - - AGC CTT ACA GGC CGG GAC AAG AAC CAG GTC GA - #G GGA GAG GTT CAG GTG 2016 Ser Leu Thr Gly Arg Asp Lys Asn Gln Val Gl - #u Gly Glu Val Gln Val 660 - # 665 - # 670 - - GTT TCC ACC GCA ACA CAA TCC TTC CTG GCG AC - #C TGC GTC AAC GGC GTG 2064 Val Ser Thr Ala Thr Gln Ser Phe Leu Ala Th - #r Cys Val Asn Gly Val 675 - # 680 - # 685 - - TGT TGG ACC GTT TAC CAT GGT GCT GGC TCA AA - #G ACC TTA GCC GCG CCA 2112 Cys Trp Thr Val Tyr His Gly Ala Gly Ser Ly - #s Thr Leu Ala Ala Pro 690 - # 695 - # 700 - - AAG GGG CCA ATC ACC CAG ATG TAC ACT AAT GT - #G GAC CAG GAC CTC GTC 2160 Lys Gly Pro Ile Thr Gln Met Tyr Thr Asn Va - #l Asp Gln Asp Leu Val 705 7 - #10 7 - #15 7 -#20 - - GGC TGG CCC AAG CCC CCC GGG GCG CGT TCC TT - #G ACA CCA TGC ACCTGT 2208 Gly Trp Pro Lys Pro Pro Gly Ala Arg Ser Le - #u Thr Pro Cys Thr Cys 725 - # 730 - # 735 - - GGC AGC TCA GAC CTT TAC TTG GTC ACG AGA CA - #T GCT GAC GTC ATT CCG 2256 Gly Ser Ser Asp Leu Tyr Leu Val Thr Arg Hi - #s Ala Asp Val Ile Pro 740 - # 745 - # 750 - - GTG CGC CGG CGG GGC GAC AGT AGG GGG AGC CT - #G CTC TCC CCC AGG CCT 2304 Val Arg Arg Arg Gly Asp Ser Arg Gly Ser Le - #u Leu Ser Pro Arg Pro 755 - # 760 - # 765 - - GTC TCC TAC TTG AAG GGC TCT TCG GGT GGT CC - #A CTG CTC TGC CCC TTC 2352 Val Ser Tyr Leu Lys Gly Ser Ser Gly Gly Pr - #o Leu Leu Cys Pro Phe 770 - # 775 - # 780 - - GGG CAC GCT GTG GGC ATC TTC CGG GCT GCC GT - #A TGC ACC CGG GGG GTT 2400 Gly His Ala Val Gly Ile Phe Arg Ala Ala Va - #l Cys Thr Arg Gly Val 785 7 - #90 7 - #95 8 -#00 - - GCG AAG GCG GTG GAC TTT GTG CCC GTA GAG TC - #C ATG GAA ACT ACTATG 2448 Ala Lys Ala Val Asp Phe Val Pro Val Glu Se - #r Met Glu Thr Thr Met 805 - # 810 - # 815 - - CGG TCT CCG GTC TTC ACG GAC AAC TCA TCC CC - #C CCG GCC GTA CCG CAG 2496 Arg Ser Pro Val Phe Thr Asp Asn Ser Ser Pr - #o Pro Ala Val Pro Gln 820 - # 825 - # 830 - - TCA TTT CAA GTG GCC CAC CTA CAC GCT CCC AC - #T GGC AGC GGC AAG AGT 2544 Ser Phe Gln Val Ala His Leu His Ala Pro Th - #r Gly Ser Gly Lys Ser 835 - # 840 - # 845 - - ACT AAA GTG CCG GCT GCA TAT GCA GCC CAA GG - #G TAC AAG GTG CTC GTC 2592 Thr Lys Val Pro Ala Ala Tyr Ala Ala Gln Gl - #y Tyr Lys Val Leu Val 850 - # 855 - # 860 - - CTC AAT CCG TCC GTT GCC GCT ACC TTA GGG TT - #T GGG GCG TAT ATG TCT 2640 Leu Asn Pro Ser Val Ala Ala Thr Leu Gly Ph - #e Gly Ala Tyr Met Ser 865 8 - #70 8 - #75 8 -#80 - - AAG GCA CAC GGT ATT GAC CCC AAC ATC AGA AC - #T GGG GTA AGG ACCATT 2688 Lys Ala His Gly Ile Asp Pro Asn Ile Arg Th - #r Gly Val Arg Thr Ile 885 - # 890 - # 895 - - ACC ACA GGC GCC CCC GTC ACA TAC TCT ACC TA - #T GGC AAG TTT CTT GCC 2736 Thr Thr Gly Ala Pro Val Thr Tyr Ser Thr Ty - #r Gly Lys Phe Leu Ala 900 - # 905 - # 910 - - GAT GGT GGT TGC TCT GGG GGC GCT TAT GAC AT - #C ATA ATA TGT GAT GAG 2784 Asp Gly Gly Cys Ser Gly Gly Ala Tyr Asp Il - #e Ile Ile Cys Asp Glu 915 - # 920 - # 925 - - TGC CAT TCA ACT GAC TCG ACT ACA ATC TTG GG - #C ATC GGC ACA GTC CTG 2832 Cys His Ser Thr Asp Ser Thr Thr Ile Leu Gl - #y Ile Gly Thr Val Leu 930 - # 935 - # 940 - - GAC CAA GCG GAG ACG GCT GGA GCG CGG CTT GT - #C GTG CTC GCC ACC GCT 2880 Asp Gln Ala Glu Thr Ala Gly Ala Arg Leu Va - #l Val Leu Ala Thr Ala 945 9 - #50 9 - #55 9 -#60 - - ACG CCT CCG GGA TCG GTC ACC GTG CCA CAC CC - #A AAC ATC GAG GAGGTG 2928 Thr Pro Pro Gly Ser Val Thr Val Pro His Pr - #o Asn Ile Glu Glu Val 965 - # 970 - # 975 - - GCC CTG TCT AAT ACT GGA GAG ATC CCC TTC TA - #T GGC AAA GCC ATC CCC 2976 Ala Leu Ser Asn Thr Gly Glu Ile Pro Phe Ty - #r Gly Lys Ala Ile Pro 980 - # 985 - # 990 - - ATT GAA GCC ATC AGG GGG GGA AGG CAT CTC AT - #T TTC TGT CAT TCC AAG 3024 Ile Glu Ala Ile Arg Gly Gly Arg His Leu Il - #e Phe Cys His Ser Lys 995 - # 1000 - # 1005 - - AAG AAG TGC GAC GAG CTC GCC GCA AAG CTG TC - #A GGC CTC GGA ATC AAC 3072 Lys Lys Cys Asp Glu Leu Ala Ala Lys Leu Se - #r Gly Leu Gly Ile Asn 1010 - # 1015 - # 1020 - - GCT GTG GCG TAT TAC CGG GGG CTC GAT GTG TC - #C GTC ATA CCA ACT ATC 3120 Ala Val Ala Tyr Tyr Arg Gly Leu Asp Val Se - #r Val Ile Pro Thr Ile 1025 1030 - # 1035 - # 1040 - - GGA GAC GTC GTT GTC GTG GCA ACA GAC GCT CT - #G ATG ACG GGC TAT ACG 3168 Gly Asp Val Val Val Val Ala Thr Asp Ala Le - #u Met Thr Gly Tyr Thr 1045 - # 1050 - # 1055 - - GGC GAC TTT GAC TCA GTG ATC GAC TGT AAC AC - #A TGT GTC ACC CAG ACA 3216 Gly Asp Phe Asp Ser Val Ile Asp Cys Asn Th - #r Cys Val Thr Gln Thr 1060 - # 1065 - # 1070 - - GTC GAC TTC AGC TTG GAT CCC ACC TTC ACC AT - #T GAG ACG ACG ACC GTG 3264 Val Asp Phe Ser Leu Asp Pro Thr Phe Thr Il - #e Glu Thr Thr Thr Val 1075 - # 1080 - # 1085 - - CCT CAA GAC GCA GTG TCG CGC TCG CAG CGG CG - #G GGT AGG ACT GGC AGG 3312 Pro Gln Asp Ala Val Ser Arg Ser Gln Arg Ar - #g Gly Arg Thr Gly Arg 1090 - # 1095 - # 1100 - - GGT AGG AGA GGC ATC TAC AGG TTT GTG ACT CC - #G GGA GAA CGG CCC TCG 3360 Gly Arg Arg Gly Ile Tyr Arg Phe Val Thr Pr - #o Gly Glu Arg Pro Ser 1105 1110 - # 1115 - # 1120 - - GGC ATG TTC GAT TCC TCG GTC CTG TGT GAG TG - #C TAT GAC GCG GGC TGT 3408 Gly Met Phe Asp Ser Ser Val Leu Cys Glu Cy - #s Tyr Asp Ala Gly Cys 1125 - # 1130 - # 1135 - - GCT TGG TAC GAG CTC ACC CCG GCC GAG ACC TC - #G GTT AGG TTG CGG GCC 3456 Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Se - #r Val Arg Leu Arg Ala 1140 - # 1145 - # 1150 - - TAC CTG AAC ACA CCA GGG TTG CCC GTT TGC CA - #G GAC CAC CTG GAG TTC 3504 Tyr Leu Asn Thr Pro Gly Leu Pro Val Cys Gl - #n Asp His Leu Glu Phe 1155 - # 1160 - # 1165 - - TGG GAG AGT GTC TTC ACA GGC CTC ACC CAT AT - #A GAT GCA CAC TTC TTG 3552 Trp Glu Ser Val Phe Thr Gly Leu Thr His Il - #e Asp Ala His Phe Leu 1170 - # 1175 - # 1180 - - TCC CAG ACC AAG CAG GCA GGA GAC AAC TTC CC - #C TAC CTG GTA GCA TAC 3600 Ser Gln Thr Lys Gln Ala Gly Asp Asn Phe Pr - #o Tyr Leu Val Ala Tyr 1185 1190 - # 1195 - # 1200 - - CAA GCC ACG GTG TGC GCC AGG GCT CAG GCC CC - #A CCT CCA TCA TGG GAT 3648 Gln Ala Thr Val Cys Ala Arg Ala Gln Ala Pr - #o Pro Pro Ser Trp Asp 1205 - # 1210 - # 1215 - - CAA ATG TGG AAG TGT CTC ATA CGG CTG AAA CC - #T ACG CTG CAC GGG CCA 3696 Gln Met Trp Lys Cys Leu Ile Arg Leu Lys Pr - #o Thr Leu His Gly Pro 1220 - # 1225 - # 1230 - - ACA CCC TTG CTG TAC AGG CTG GGA GCC GTC CA - #G AAT GAG GTC ACC CTC 3744 Thr Pro Leu Leu Tyr Arg Leu Gly Ala Val Gl - #n Asn Glu Val Thr Leu 1235 - # 1240 - # 1245 - - ACC CAC CCC ATA ACC AAA TAC ATC ATG GCA TG - #C ATG TCG GCT GAC CTG 3792 Thr His Pro Ile Thr Lys Tyr Ile Met Ala Cy - #s Met Ser Ala Asp Leu 1250 - # 1255 - # 1260 - - GAG GTC GTC ACT AGC ACC TGG GTG CTG GTG GG - #C GGA GTC CTT GCA GCT 3840 Glu Val Val Thr Ser Thr Trp Val Leu Val Gl - #y Gly Val Leu Ala Ala 1265 1270 - # 1275 - # 1280 - - CTG GCC GCG TAT TGC CTG ACA ACA GGC AGT GT - #G GTC ATT GTG GGT AGG 3888 Leu Ala Ala Tyr Cys Leu Thr Thr Gly Ser Va - #l Val Ile Val Gly Arg 1285 - # 1290 - # 1295 - - ATT ATC TTG TCC GGG AGG CCG GCC ATT GTT CC - #C GAC AGG GAG CTT CTC 3936 Ile Ile Leu Ser Gly Arg Pro Ala Ile Val Pr - #o Asp Arg Glu Leu Leu 1300 - # 1305 - # 1310 - - TAC CAG GAG TTC GAT GAA ATG GAA GAG TGC GC - #C TCG CAC CTC CCT TAC 3984 Tyr Gln Glu Phe Asp Glu Met Glu Glu Cys Al - #a Ser His Leu Pro Tyr 1315 - # 1320 - # 1325 - - ATC GAG CAG GGA ATG CAG CTC GCC GAG CAA TT - #C AAG CAG AAA GCG CTC 4032 Ile Glu Gln Gly Met Gln Leu Ala Glu Gln Ph - #e Lys Gln Lys Ala Leu 1330 - # 1335 - # 1340 - - GGG TTA CTG CAA ACA GCC ACC AAA CAA GCG GA - #G GCT GCT GCT CCC GTG 4080 Gly Leu Leu Gln Thr Ala Thr Lys Gln Ala Gl - #u Ala Ala Ala Pro Val 1345 1350 - # 1355 - # 1360 - - GTG GAG TCC AAG TGG CGA GCC CTT GAG ACA TT - #C TGG GCG AAG CAC ATG 4128 Val Glu Ser Lys Trp Arg Ala Leu Glu Thr Ph - #e Trp Ala Lys His Met 1365 - # 1370 - # 1375 - - TGG AAT TTC ATC AGC GGG ATA CAG TAC TTA GC - #A GGC TTA TCC ACT CTG 4176 Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu Al - #a Gly Leu Ser Thr Leu 1380 - # 1385 - # 1390 - - CCT GGG AAC CCC GCA ATA GCA TCA TTG ATG GC - #A TTC ACA GCC TCT ATC 4224 Pro Gly Asn Pro Ala Ile Ala Ser Leu Met Al - #a Phe Thr Ala Ser Ile 1395 - # 1400 - # 1405 - - ACC AGC CCG CTC ACC ACC CAA AGT ACC CTC CT - #G TTT AAC ATC TTG GGG 4272 Thr Ser Pro Leu Thr Thr Gln Ser Thr Leu Le - #u Phe Asn Ile Leu Gly 1410 - # 1415 - # 1420 - - GGG TGG GTG GCT GCC CAA CTC GCC CCC CCC AG - #C GCC GCT TCG GCT TTC 4320 Gly Trp Val Ala Ala Gln Leu Ala Pro Pro Se - #r Ala Ala Ser Ala Phe 1425 1430 - # 1435 - # 1440 - - GTG GGC GCC GGC ATC GCC GGT GCG GCT GTT GG - #C AGC ATA GGC CTT GGG 4368 Val Gly Ala Gly Ile Ala Gly Ala Ala Val Gl - #y Ser Ile Gly Leu Gly 1445 - # 1450 - # 1455 - - AAG GTG CTT GTG GAC ATT CTG GCG GGT TAT GG - #A GCA GGA GTG GCC GGC 4416 Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gl - #y Ala Gly Val Ala Gly 1460 - # 1465 - # 1470 - - GCG CTC GTG GCC TTT AAG GTC ATG AGC GGC GA - #G ATG CCC TCC ACC GAG 4464 Ala Leu Val Ala Phe Lys Val Met Ser Gly Gl - #u Met Pro Ser Thr Glu 1475 - # 1480 - # 1485 - - GAC CTG GTC AAT CTA CTT CCT GCC ATC CTC TC - #T CCT GGC GCC CTG GTC 4512 Asp Leu Val Asn Leu Leu Pro Ala Ile Leu Se - #r Pro Gly Ala Leu Val 1490 - # 1495 - # 1500 - - GTC GGG GTC GTG TGT GCA GCA ATA CTG CGT CG - #A CAC GTG GGT CCG GGA 4560 Val Gly Val Val Cys Ala Ala Ile Leu Arg Ar - #g His Val Gly Pro Gly 1505 1510 - # 1515 - # 1520 - - GAG GGG GCT GTG CAG TGG ATG AAC CGG CTG AT - #A GCG TTC GCC TCG CGG 4608 Glu Gly Ala Val Gln Trp Met Asn Arg Leu Il - #e Ala Phe Ala Ser Arg 1525 - # 1530 - # 1535 - - GGT AAT CAT GTT TCC CCC ACG CAC TAT GTG CC - #T GAG AGC GAC GCC GCA 4656 Gly Asn His Val Ser Pro Thr His Tyr Val Pr - #o Glu Ser Asp Ala Ala 1540 - # 1545 - # 1550 - - GCG CGT GTT ACT CAG ATC CTC TCC AGC CTT AC - #C ATC ACT CAG CTG CTG 4704 Ala Arg Val Thr Gln Ile Leu Ser Ser Leu Th - #r Ile Thr Gln Leu Leu 1555 - # 1560 - # 1565 - - AAA AGG CTC CAC CAG TGG ATT AAT GAA GAC TG - #C TCC ACA CCG TGT TCC 4752 Lys Arg Leu His Gln Trp Ile Asn Glu Asp Cy - #s Ser Thr Pro Cys Ser 1570 - # 1575 - # 1580 - - GGC TCG TGG CTA AGG GAT GTT TGG GAC TGG AT - #A TGC ACG GTG TTG ACT 4800 Gly Ser Trp Leu Arg Asp Val Trp Asp Trp Il - #e Cys Thr Val Leu Thr 1585 1590 - # 1595 - # 1600 - - GAC TTC AAG ACC TGG CTC CAG TCC AAG CTC CT - #G CCG CAG CTA CCT GGA 4848 Asp Phe Lys Thr Trp Leu Gln Ser Lys Leu Le - #u Pro Gln Leu Pro Gly 1605 - # 1610 - # 1615 - - GTC CCT TTT TTC TCG TGC CAA CGC GGG TAC AA - #G GGA GTC TGG CGG GGA 4896 Val Pro Phe Phe Ser Cys Gln Arg Gly Tyr Ly - #s Gly Val Trp Arg Gly 1620 - # 1625 - # 1630 - - GAC GGC ATC ATG CAA ACC ACC TGC CCA TGT GG - #A GCA CAG ATC ACC GGA 4944 Asp Gly Ile Met Gln Thr Thr Cys Pro Cys Gl - #y Ala Gln Ile Thr Gly 1635 - # 1640 - # 1645 - - CAT GTC AAA AAC GGT TCC ATG AGG ATC GTC GG - #G CCT AAG ACC TGC AGC 4992 His Val Lys Asn Gly Ser Met Arg Ile Val Gl - #y Pro Lys Thr Cys Ser 1650 - # 1655 - # 1660 - - AAC ACG TGG CAT GGA ACA TTC CCC ATC AAC GC - #A TAC ACC ACG GGC CCC 5040 Asn Thr Trp His Gly Thr Phe Pro Ile Asn Al - #a Tyr Thr Thr Gly Pro 1665 1670 - # 1675 - # 1680 - - TGC ACA CCC TCT CCA GCG CCA AAC TAT TCT AG - #G GCG CTG TGG CGG GTG 5088 Cys Thr Pro Ser Pro Ala Pro Asn Tyr Ser Ar - #g Ala Leu Trp Arg Val 1685 - # 1690 - # 1695 - - GCC GCT GAG GAG TAC GTG GAG GTC ACG CGG GT - #G GGG GAT TTC CAC TAC 5136 Ala Ala Glu Glu Tyr Val Glu Val Thr Arg Va - #l Gly Asp Phe His Tyr 1700 - # 1705 - # 1710 - - GTG ACG GGC ATG ACC ACT GAC AAC GTA AAG TG - #C CCA TGC CAG GTT CCG 5184 Val Thr Gly Met Thr Thr Asp Asn Val Lys Cy - #s Pro Cys Gln Val Pro 1715 - # 1720 - # 1725 - - GCT CCT GAA TTC TTC TCG GAG GTG GAC GGA GT - #G CGG TTG CAC AGG TAC 5232 Ala Pro Glu Phe Phe Ser Glu Val Asp Gly Va - #l Arg Leu His Arg Tyr 1730 - # 1735 - # 1740 - - GCT CCG GCG TGC AGG CCT CTC CTA CGG GAG GA - #G GTT ACA TTC CAG GTC 5280 Ala Pro Ala Cys Arg Pro Leu Leu Arg Glu Gl - #u Val Thr Phe Gln Val 1745 1750 - # 1755 - # 1760 - - GGG CTC AAC CAA TAC CTG GTT GGG TCA CAG CT - #A CCA TGC GAG CCC GAA 5328 Gly Leu Asn Gln Tyr Leu Val Gly Ser Gln Le - #u Pro Cys Glu Pro Glu 1765 - # 1770 - # 1775 - - CCG GAT GTA GCA GTG CTC ACT TCC ATG CTC AC - #C GAC CCC TCC CAC ATC 5376 Pro Asp Val Ala Val Leu Thr Ser Met Leu Th - #r Asp Pro Ser His Ile 1780 - # 1785 - # 1790 - - ACA GCA GAA ACG GCT AAG CGT AGG TTG GCC AG - #G GGG TCT CCC CCC TCC 5424 Thr Ala Glu Thr Ala Lys Arg Arg Leu Ala Ar - #g Gly Ser Pro Pro Ser 1795 - # 1800 - # 1805 - - TTG GCC AGC TCT TCA GCT AGC CAG TTG TCT GC - #G CCT TCC TTG AAG GCG 5472 Leu Ala Ser Ser Ser Ala Ser Gln Leu Ser Al - #a Pro Ser Leu Lys Ala 1810 - # 1815 - # 1820 - - ACA TGC ACT ACC CAC CAT GTC TCT CCG GAC GC - #T GAC CTC ATC GAG GCC 5520 Thr Cys Thr Thr His His Val Ser Pro Asp Al - #a Asp Leu Ile Glu Ala 1825 1830 - # 1835 - # 1840 - - AAC CTC CTG TGG CGG CAG GAG ATG GGC GGG AA - #C ATC ACC CGC GTG GAG 5568 Asn Leu Leu Trp Arg Gln Glu Met Gly Gly As - #n Ile Thr Arg Val Glu 1845 - # 1850 - # 1855 - - TCG GAG AAC AAG GTG GTA GTC CTG GAC TCT TT - #C GAC CCG CTT CGA GCG 5616 Ser Glu Asn Lys Val Val Val Leu Asp Ser Ph - #e Asp Pro Leu Arg Ala 1860 - # 1865 - # 1870 - - GAG GAG GAT GAG AGG GAA GTA TCC GTT CCG GC - #G GAG ATC CTG CGG AAA 5664 Glu Glu Asp Glu Arg Glu Val Ser Val Pro Al - #a Glu Ile Leu Arg Lys 1875 - # 1880 - # 1885 - - TCC AAG AAG TTC CCC GCA GCG ATG CCC ATC TG - #G GCG CGC CCG GAT TAC 5712 Ser Lys Lys Phe Pro Ala Ala Met Pro Ile Tr - #p Ala Arg Pro Asp Tyr 1890 - # 1895 - # 1900 - - AAC CCT CCA CTG TTA GAG TCC TGG AAG GAC CC - #G GAC TAC GTC CCT CCG 5760 Asn Pro Pro Leu Leu Glu Ser Trp Lys Asp Pr - #o Asp Tyr Val Pro Pro 1905 1910 - # 1915 - # 1920 - - GTG GTG CAC GGG TGC CCG TTG CCA CCT ATC AA - #G GCC CCT CCA ATA CCA 5808 Val Val His Gly Cys Pro Leu Pro Pro Ile Ly - #s Ala Pro Pro Ile Pro 1925 - # 1930 - # 1935 - - CCT CCA CGG AGA AAG AGG ACG GTT GTC CTA AC - #A GAG TCC TCC GTG TCT 5856 Pro Pro Arg Arg Lys Arg Thr Val Val Leu Th - #r Glu Ser Ser Val Ser 1940 - # 1945 - # 1950 - - TCT GCC TTA GCG GAG CTC GCT ACT AAG ACC TT - #C GGC AGC TCC GAA TCA 5904 Ser Ala Leu Ala Glu Leu Ala Thr Lys Thr Ph - #e Gly Ser Ser Glu Ser 1955 - # 1960 - # 1965 - - TCG GCC GTC GAC AGC GGC ACG GCG ACC GCC CT - #T CCT GAC CAG GCC TCC 5952 Ser Ala Val Asp Ser Gly Thr Ala Thr Ala Le - #u Pro Asp Gln Ala Ser 1970 - # 1975 - # 1980 - - GAC GAC GGT GAC AAA GGA TCC GAC GTT GAG TC - #G TAC TCC TCC ATG CCC 6000 Asp Asp Gly Asp Lys Gly Ser Asp Val Glu Se - #r Tyr Ser Ser Met Pro 1985 1990 - # 1995 - # 2000 - - CCC CTT GAG GGG GAA CCG GGG GAC CCC GAT CT - #C AGT GAC GGG TCT TGG 6048 Pro Leu Glu Gly Glu Pro Gly Asp Pro Asp Le - #u Ser Asp Gly Ser Trp 2005 - # 2010 - # 2015 - - TCT ACC GTG AGC GAG GAA GCT AGT GAG GAT GT - #C GTC TGC TGC TCA ATG 6096 Ser Thr Val Ser Glu Glu Ala Ser Glu Asp Va - #l Val Cys Cys Ser Met 2020 - # 2025 - # 2030 - - TCC TAC ACA TGG ACA GGC GCC TTG ATC ACG CC - #A TGC GCT GCG GAG GAA 6144 Ser Tyr Thr Trp Thr Gly Ala Leu Ile Thr Pr - #o Cys Ala Ala Glu Glu 2035 - # 2040 - # 2045 - - AGC AAG CTG CCC ATC AAC GCG TTG AGC AAC TC - #T TTG CTG CGC CAC CAT 6192 Ser Lys Leu Pro Ile Asn Ala Leu Ser Asn Se - #r Leu Leu Arg His His 2050 - # 2055 - # 2060 - - AAC ATG GTT TAT GCC ACA ACA TCT CGC AGC GC - #A GGC CTG CGG CAG AAG 6240 Asn Met Val Tyr Ala Thr Thr Ser Arg Ser Al - #a Gly Leu Arg Gln Lys 2065 2070 - # 2075 - # 2080 - - AAG GTC ACC TTT GAC AGA CTG CAA GTC CTG GA - #C GAC CAC TAC CGG GAC 6288 Lys Val Thr Phe Asp Arg Leu Gln Val Leu As - #p Asp His Tyr Arg Asp 2085 - # 2090 - # 2095 - - GTG CTC AAG GAG ATG AAG GCG AAG GCG TCC AC - #A GTT AAG GCT AAA CTC 6336 Val Leu Lys Glu Met Lys Ala Lys Ala Ser Th - #r Val Lys Ala Lys Leu 2100 - # 2105 - # 2110 - - CTA TCC GTA GAG GAA GCC TGC AAG CTG ACG CC - #C CCA CAT TCG GCC AAA 6384 Leu Ser Val Glu Glu Ala Cys Lys Leu Thr Pr - #o Pro His Ser Ala Lys 2115 - # 2120 - # 2125 - - TCC AAG TTT GGC TAT GGG GCA AAG GAC GTC CG - #G AAC CTA TCC AGC AAG 6432 Ser Lys Phe Gly Tyr Gly Ala Lys Asp Val Ar - #g Asn Leu Ser Ser Lys 2130 - # 2135 - # 2140 - - GCC GTT AAC CAC ATC CAC TCC GTG TGG AAG GA - #C TTG CTG GAA GAC ACT 6480 Ala Val Asn His Ile His Ser Val Trp Lys As - #p Leu Leu Glu Asp Thr 2145 2150 - # 2155 - # 2160 - - GTG ACA CCA ATT GAC ACC ACC ATC ATG GCA AA - #A AAT GAG GTT TTC TGT 6528 Val Thr Pro Ile Asp Thr Thr Ile Met Ala Ly - #s Asn Glu Val Phe Cys 2165 - # 2170 - # 2175 - - GTC CAA CCA GAG AAA GGA GGC CGT AAG CCA GC - #C CGC CTT ATC GTA TTC 6576 Val Gln Pro Glu Lys Gly Gly Arg Lys Pro Al - #a Arg Leu Ile Val Phe 2180 - # 2185 - # 2190 - - CCA GAT CTG GGA GTC CGT GTA TGC GAG AAG AT - #G GCC CTC TAT GAT GTG 6624 Pro Asp Leu Gly Val Arg Val Cys Glu Lys Me - #t Ala Leu Tyr Asp Val 2195 - # 2200 - # 2205 - - GTC TCC ACC CTT CCT CAG GTC GTG ATG GGC TC - #C TCA TAC GGA TTC CAG 6672 Val Ser Thr Leu Pro Gln Val Val Met Gly Se - #r Ser Tyr Gly Phe Gln 2210 - # 2215 - # 2220 - - TAC TCT CCT GGG CAG CGA GTC GAG TTC CTG GT - #G AAT ACC TGG AAA TCA 6720 Tyr Ser Pro Gly Gln Arg Val Glu Phe Leu Va - #l Asn Thr Trp Lys Ser 2225 2230 - # 2235 - # 2240 - - AAG AAA AAC CCC ATG GGC TTT TCA TAT GAC AC - #T CGC TGT TTC GAC TCA 6768 Lys Lys Asn Pro Met Gly Phe Ser Tyr Asp Th - #r Arg Cys Phe Asp Ser 2245 - # 2250 - # 2255 - - ACG GTC ACC GAG AAC GAC ATC CGT GTT GAG GA - #G TCA ATT TAC CAA TGT 6816 Thr Val Thr Glu Asn Asp Ile Arg Val Glu Gl - #u Ser Ile Tyr Gln Cys 2260 - # 2265 - # 2270 - - TGT GAC TTG GCC CCC GAA GCC AGA CAG GCC AT - #A AAA TCG CTC ACA GAG 6864 Cys Asp Leu Ala Pro Glu Ala Arg Gln Ala Il - #e Lys Ser Leu Thr Glu 2275 - # 2280 - # 2285 - - CGG CTT TAT ATC GGG GGT CCT CTG ACT AAT TC - #A AAA GGG CAG AAC TGC 6912 Arg Leu Tyr Ile Gly Gly Pro Leu Thr Asn Se - #r Lys Gly Gln Asn Cys 2290 - # 2295 - # 2300 - - GGT TAT CGC CGG TGC CGC GCG AGC GGC GTG CT - #G ACG ACT AGC TGC GGT 6960 Gly Tyr Arg Arg Cys Arg Ala Ser Gly Val Le - #u Thr Thr Ser Cys Gly 2305 2310 - # 2315 - # 2320 - - AAC ACC CTC ACA TGT TAC TTG AAG GCC TCT GC - #A GCC TGT CGA GCT GCG 7008 Asn Thr Leu Thr Cys Tyr Leu Lys Ala Ser Al - #a Ala Cys Arg Ala Ala 2325 - # 2330 - # 2335 - - AAG CTC CAG GAC TGC ACG ATG CTC GTG AAC GG - #A GAC GAC CTC GTC GTT 7056 Lys Leu Gln Asp Cys Thr Met Leu Val Asn Gl - #y Asp Asp Leu Val Val 2340 - # 2345 - # 2350 - - ATC TGT GAA AGC GCG GGA ACC CAA GAG GAC GC - #G GCG AGC CTA CGA GTC 7104 Ile Cys Glu Ser Ala Gly Thr Gln Glu Asp Al - #a Ala Ser Leu Arg Val 2355 - # 2360 - # 2365 - - TTC ACG GAG GCT ATG ACT AGG TAC TCC GCC CC - #C CCC GGG GAC CCG CCC 7152 Phe Thr Glu Ala Met Thr Arg Tyr Ser Ala Pr - #o Pro Gly Asp Pro Pro 2370 - # 2375 - # 2380 - - CAA CCA GAA TAC GAC TTG GAG CTG ATA ACA TC - #A TGT TCC TCC AAT GTG 7200 Gln Pro Glu Tyr Asp Leu Glu Leu Ile Thr Se - #r Cys Ser Ser Asn Val 2385 2390 - # 2395 - # 2400 - - TCG GTC GCC CAC GAT GCA TCA GGC AAA AGG GT - #G TAC TAC CTC ACC CGT 7248 Ser Val Ala His Asp Ala Ser Gly Lys Arg Va - #l Tyr Tyr Leu Thr Arg 2405 - # 2410 - # 2415 - - GAT CCC ACC ACC CCC CTA GCA CGG GCT GCG TG - #G GAG ACA GCT AGA CAC 7296 Asp Pro Thr Thr Pro Leu Ala Arg Ala Ala Tr - #p Glu Thr Ala Arg His 2420 - # 2425 - # 2430 - - ACT CCA GTT AAC TCC TGG CTA GGC AAC ATT AT - #T ATG TAT GCG CCC ACT 7344 Thr Pro Val Asn Ser Trp Leu Gly Asn Ile Il - #e Met Tyr Ala Pro Thr 2435 - # 2440 - # 2445 - - TTG TGG GCA AGG ATG ATT CTG ATG ACT CAC TT - #C TTC TCC ATC CTT CTA 7392 Leu Trp Ala Arg Met Ile Leu Met Thr His Ph - #e Phe Ser Ile Leu Leu 2450 - # 2455 - # 2460 - - GCG CAG GAG CAA CTT GAA AAA GCC CTG GAC TG - #C CAG ATC TAC GGG GCC 7440 Ala Gln Glu Gln Leu Glu Lys Ala Leu Asp Cy - #s Gln Ile Tyr Gly Ala 2465 2470 - # 2475 - # 2480 - - TGT TAC TCC ATT GAG CCA CTT GAC CTA CCT CA - #G ATC ATT GAA CGA CTC 7488 Cys Tyr Ser Ile Glu Pro Leu Asp Leu Pro Gl - #n Ile Ile Glu Arg Leu 2485 - # 2490 - # 2495 - - CAT GGC CTT AGC GCA TTT TCA CTC CAT AGT TA - #C TCT CCA GGT GAG ATC 7536 His Gly Leu Ser Ala Phe Ser Leu His Ser Ty - #r Ser Pro Gly Glu Ile 2500 - # 2505 - # 2510 - - AAT AGG GTG GCT TCA TGC CTC AGG AAA CTT GG - #G GTA CCA CCC TTG CGA 7584 Asn Arg Val Ala Ser Cys Leu Arg Lys Leu Gl - #y Val Pro Pro Leu Arg 2515 - # 2520 - # 2525 - - GTC TGG AGA CAT CGG GCC AGG AGC GTC CGC GC - #T AGG CTA CTG TCC CAG 7632 Val Trp Arg His Arg Ala Arg Ser Val Arg Al - #a Arg Leu Leu Ser Gln 2530 - # 2535 - # 2540 - - GGA GGG AGG GCC GCC ACT TGT GGC AAA TAC CT - #C TTC AAC TGG GCA GTA 7680 Gly Gly Arg Ala Ala Thr Cys Gly Lys Tyr Le - #u Phe Asn Trp Ala Val 2545 2550 - # 2555 - # 2560 - - AAA ACC AAA CTT AAA CTC ACT CCA ATC CCG GC - #T GCG TCC CGG CTG GAC 7728 Lys Thr Lys Leu Lys Leu Thr Pro Ile Pro Al - #a Ala Ser Arg Leu Asp 2565 - # 2570 - # 2575 - - TTG TCC GGC TGG TTC GTT GCT GGT TAC AGC GG - #G GGA GAC ATA TAT CAC 7776 Leu Ser Gly Trp Phe Val Ala Gly Tyr Ser Gl - #y Gly Asp Ile Tyr His 2580 - # 2585 - # 2590 - - AGC CTG TCT CGT GCC CGA CCC CGT TGG TTC AT - #G CTG TGC CTA CTC CTA 7824 Ser Leu Ser Arg Ala Arg Pro Arg Trp Phe Me - #t Leu Cys Leu Leu Leu 2595 - # 2600 - # 2605 - - CTT TCT GTA GGG GTA GGC ATC TAC CTG CTC CC - #C AAC CGA - # 7863 Leu Ser Val Gly Val Gly Ile Tyr Leu Leu Pr - #o Asn Arg 2610 - # 2615 - # 2620 - - - - (2) INFORMATION FOR SEQ ID NO:36: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2621 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:36: - - Gly Ala Gln Ala Lys Thr Thr Asn Arg Leu Va - #l Ser Met Phe Ala Ser 1 5 - # 10 - # 15 - - Gly Pro Ser Gln Lys Ile Gln Leu Ile Asn Th - #r Asn Gly Ser Trp His 20 - # 25 - # 30 - - Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp Se - #r Leu Gln Thr Gly Phe 35 - # 40 - # 45 - - Leu Ala Ala Leu Phe Tyr Thr His Ser Phe As - #n Ser Ser Gly Cys Pro 50 - # 55 - # 60 - - Glu Arg Met Ala Gln Cys Arg Thr Ile Asp Ly - #s Phe Asp Gln Gly Trp 65 - # 70 - # 75 - # 80 - - Gly Pro Ile Thr Tyr Ala Glu Ser Ser Arg Se - #r Asp Gln Arg Pro Tyr 85 - # 90 - # 95 - - Cys Trp His Tyr Pro Pro Pro Gln Cys Thr Il - #e Val Pro Ala Ser Glu 100 - # 105 - # 110 - - Val Cys Gly Pro Val Tyr Cys Phe Thr Pro Se - #r Pro Val Val Val Gly 115 - # 120 - # 125 - - Thr Thr Asp Arg Phe Gly Val Pro Thr Tyr Ar - #g Trp Gly Glu Asn Glu 130 - # 135 - # 140 - - Thr Asp Val Leu Leu Leu Asn Asn Thr Arg Pr - #o Pro Gln Gly Asn Trp 145 1 - #50 1 - #55 1 -#60 - - Phe Gly Cys Thr Trp Met Asn Ser Thr Gly Ph - #e Thr Lys Thr CysGly 165 - # 170 - # 175 - - Gly Pro Pro Cys Asn Ile Gly Gly Val Gly As - #n Asn Thr Leu Thr Cys 180 - # 185 - # 190 - - Pro Thr Asp Cys Phe Arg Lys His Pro Glu Al - #a Thr Tyr Thr Lys Cys 195 - # 200 - # 205 - - Gly Ser Gly Pro Trp Leu Thr Pro Arg Cys Me - #t Val Asp Tyr Pro Tyr 210 - # 215 - # 220 - - Arg Leu Trp His Tyr Pro Cys Thr Val Asn Ph - #e Thr Ile Phe Lys Val 225 2 - #30 2 - #35 2 -#40 - - Arg Met Tyr Val Gly Gly Val Glu His Arg Le - #u Asn Ala Ala CysAsn 245 - # 250 - # 255 - - Trp Thr Arg Gly Glu Arg Cys Asp Leu Glu As - #p Arg Asp Arg Pro Glu 260 - # 265 - # 270 - - Leu Ser Pro Leu Leu Leu Ser Thr Thr Glu Tr - #p Gln Val Leu Pro Cys 275 - # 280 - # 285 - - Ser Phe Thr Thr Leu Pro Ala Leu Ser Thr Gl - #y Leu Ile His Leu His 290 - # 295 - # 300 - - Gln Asn Ile Val Asp Val Gln Tyr Leu Tyr Gl - #y Ile Gly Ser Ala Val 305 3 - #10 3 - #15 3 -#20 - - Val Ser Phe Ala Ile Lys Trp Glu Tyr Val Le - #u Leu Leu Phe LeuLeu 325 - # 330 - # 335 - - Leu Ala Asp Ala Arg Val Cys Ala Cys Leu Tr - #p Met Met Leu Leu Ile 340 - # 345 - # 350 - - Ala Gln Ala Glu Ala Ala Leu Glu Asn Leu Va - #l Val Leu Asn Ser Ala 355 - # 360 - # 365 - - Ser Val Ala Gly Ala His Gly Ile Leu Ser Ph - #e Leu Val Phe Phe Cys 370 - # 375 - # 380 - - Ala Ala Trp Tyr Ile Lys Gly Arg Leu Val Pr - #o Gly Ala Thr Tyr Ala 385 3 - #90 3 - #95 4 -#00 - - Leu Tyr Gly Val Trp Pro Leu Leu Leu Leu Le - #u Leu Ala Leu ProPro 405 - # 410 - # 415 - - Arg Ala Tyr Ala Met Asp Arg Glu Met Ala Al - #a Ser Cys Gly Gly Ala 420 - # 425 - # 430 - - Val Phe Val Gly Leu Val Leu Leu Thr Leu Se - #r Pro Tyr Tyr Lys Val 435 - # 440 - # 445 - - Phe Leu Ala Arg Leu Ile Trp Trp Leu Gln Ty - #r Phe Thr Thr Arg Ala 450 - # 455 - # 460 - - Glu Ala Asp Leu His Val Trp Ile Pro Pro Le - #u Asn Ala Arg Gly Gly 465 4 - #70 4 - #75 4 -#80 - - Arg Asp Ala Ile Ile Leu Leu Met Cys Ala Va - #l His Pro Glu LeuIle 485 - # 490 - # 495 - - Phe Asp Ile Thr Lys Leu Leu Ile Ala Ile Le - #u Gly Pro Leu Met Val 500 - # 505 - # 510 - - Leu Gln Ala Gly Ile Thr Arg Val Pro Tyr Ph - #e Val Arg Ala Gln Gly 515 - # 520 - # 525 - - Leu Ile His Ala Cys Met Leu Val Arg Lys Va - #l Ala Gly Gly His Tyr 530 - # 535 - # 540 - - Val Gln Met Ala Phe Met Lys Leu Gly Ala Le - #u Thr Gly Thr Tyr Ile 545 5 - #50 5 - #55 5 -#60 - - Tyr Asn His Leu Thr Pro Leu Arg Asp Trp Pr - #o Arg Ala Gly LeuArg 565 - # 570 - # 575 - - Asp Leu Ala Val Ala Val Glu Pro Val Val Ph - #e Ser Asp Met Glu Thr 580 - # 585 - # 590 - - Lys Ile Ile Thr Trp Gly Ala Asp Thr Ala Al - #a Cys Gly Asp Ile Ile 595 - # 600 - # 605 - - Leu Gly Leu Pro Val Ser Ala Arg Arg Gly Ly - #s Glu Ile Leu Leu Gly 610 - # 615 - # 620 - - Pro Ala Asp Ser Leu Glu Gly Arg Gly Leu Ar - #g Leu Leu Ala Pro Ile 625 6 - #30 6 - #35 6 -#40 - - Thr Ala Tyr Ser Gln Gln Thr Arg Gly Leu Le - #u Gly Cys Ile IleThr 645 - # 650 - # 655 - - Ser Leu Thr Gly Arg Asp Lys Asn Gln Val Gl - #u Gly Glu Val Gln Val 660 - # 665 - # 670 - - Val Ser Thr Ala Thr Gln Ser Phe Leu Ala Th - #r Cys Val Asn Gly Val 675 - # 680 - # 685 - - Cys Trp Thr Val Tyr His Gly Ala Gly Ser Ly - #s Thr Leu Ala Ala Pro 690 - # 695 - # 700 - - Lys Gly Pro Ile Thr Gln Met Tyr Thr Asn Va - #l Asp Gln Asp Leu Val 705 7 - #10 7 - #15 7 -#20 - - Gly Trp Pro Lys Pro Pro Gly Ala Arg Ser Le - #u Thr Pro Cys ThrCys 725 - # 730 - # 735 - - Gly Ser Ser Asp Leu Tyr Leu Val Thr Arg Hi - #s Ala Asp Val Ile Pro 740 - # 745 - # 750 - - Val Arg Arg Arg Gly Asp Ser Arg Gly Ser Le - #u Leu Ser Pro Arg Pro 755 - # 760 - # 765 - - Val Ser Tyr Leu Lys Gly Ser Ser Gly Gly Pr - #o Leu Leu Cys Pro Phe 770 - # 775 - # 780 - - Gly His Ala Val Gly Ile Phe Arg Ala Ala Va - #l Cys Thr Arg Gly Val 785 7 - #90 7 - #95 8 -#00 - - Ala Lys Ala Val Asp Phe Val Pro Val Glu Se - #r Met Glu Thr ThrMet 805 - # 810 - # 815 - - Arg Ser Pro Val Phe Thr Asp Asn Ser Ser Pr - #o Pro Ala Val Pro Gln 820 - # 825 - # 830 - - Ser Phe Gln Val Ala His Leu His Ala Pro Th - #r Gly Ser Gly Lys Ser 835 - # 840 - # 845 - - Thr Lys Val Pro Ala Ala Tyr Ala Ala Gln Gl - #y Tyr Lys Val Leu Val 850 - # 855 - # 860 - - Leu Asn Pro Ser Val Ala Ala Thr Leu Gly Ph - #e Gly Ala Tyr Met Ser 865 8 - #70 8 - #75 8 -#80 - - Lys Ala His Gly Ile Asp Pro Asn Ile Arg Th - #r Gly Val Arg ThrIle 885 - # 890 - # 895 - - Thr Thr Gly Ala Pro Val Thr Tyr Ser Thr Ty - #r Gly Lys Phe Leu Ala 900 - # 905 - # 910 - - Asp Gly Gly Cys Ser Gly Gly Ala Tyr Asp Il - #e Ile Ile Cys Asp Glu 915 - # 920 - # 925 - - Cys His Ser Thr Asp Ser Thr Thr Ile Leu Gl - #y Ile Gly Thr Val Leu 930 - # 935 - # 940 - - Asp Gln Ala Glu Thr Ala Gly Ala Arg Leu Va - #l Val Leu Ala Thr Ala 945 9 - #50 9 - #55 9 -#60 - - Thr Pro Pro Gly Ser Val Thr Val Pro His Pr - #o Asn Ile Glu GluVal 965 - # 970 - # 975 - - Ala Leu Ser Asn Thr Gly Glu Ile Pro Phe Ty - #r Gly Lys Ala Ile Pro 980 - # 985 - # 990 - - Ile Glu Ala Ile Arg Gly Gly Arg His Leu Il - #e Phe Cys His Ser Lys 995 - # 1000 - # 1005 - - Lys Lys Cys Asp Glu Leu Ala Ala Lys Leu Se - #r Gly Leu Gly Ile Asn 1010 - # 1015 - # 1020 - - Ala Val Ala Tyr Tyr Arg Gly Leu Asp Val Se - #r Val Ile Pro Thr Ile 1025 1030 - # 1035 - # 1040 - - Gly Asp Val Val Val Val Ala Thr Asp Ala Le - #u Met Thr Gly Tyr Thr 1045 - # 1050 - # 1055 - - Gly Asp Phe Asp Ser Val Ile Asp Cys Asn Th - #r Cys Val Thr Gln Thr 1060 - # 1065 - # 1070 - - Val Asp Phe Ser Leu Asp Pro Thr Phe Thr Il - #e Glu Thr Thr Thr Val 1075 - # 1080 - # 1085 - - Pro Gln Asp Ala Val Ser Arg Ser Gln Arg Ar - #g Gly Arg Thr Gly Arg 1090 - # 1095 - # 1100 - - Gly Arg Arg Gly Ile Tyr Arg Phe Val Thr Pr - #o Gly Glu Arg Pro Ser 1105 1110 - # 1115 - # 1120 - - Gly Met Phe Asp Ser Ser Val Leu Cys Glu Cy - #s Tyr Asp Ala Gly Cys 1125 - # 1130 - # 1135 - - Ala Trp Tyr Glu Leu Thr Pro Ala Glu Thr Se - #r Val Arg Leu Arg Ala 1140 - # 1145 - # 1150 - - Tyr Leu Asn Thr Pro Gly Leu Pro Val Cys Gl - #n Asp His Leu Glu Phe 1155 - # 1160 - # 1165 - - Trp Glu Ser Val Phe Thr Gly Leu Thr His Il - #e Asp Ala His Phe Leu 1170 - # 1175 - # 1180 - - Ser Gln Thr Lys Gln Ala Gly Asp Asn Phe Pr - #o Tyr Leu Val Ala Tyr 1185 1190 - # 1195 - # 1200 - - Gln Ala Thr Val Cys Ala Arg Ala Gln Ala Pr - #o Pro Pro Ser Trp Asp 1205 - # 1210 - # 1215 - - Gln Met Trp Lys Cys Leu Ile Arg Leu Lys Pr - #o Thr Leu His Gly Pro 1220 - # 1225 - # 1230 - - Thr Pro Leu Leu Tyr Arg Leu Gly Ala Val Gl - #n Asn Glu Val Thr Leu 1235 - # 1240 - # 1245 - - Thr His Pro Ile Thr Lys Tyr Ile Met Ala Cy - #s Met Ser Ala Asp Leu 1250 - # 1255 - # 1260 - - Glu Val Val Thr Ser Thr Trp Val Leu Val Gl - #y Gly Val Leu Ala Ala 1265 1270 - # 1275 - # 1280 - - Leu Ala Ala Tyr Cys Leu Thr Thr Gly Ser Va - #l Val Ile Val Gly Arg 1285 - # 1290 - # 1295 - - Ile Ile Leu Ser Gly Arg Pro Ala Ile Val Pr - #o Asp Arg Glu Leu Leu 1300 - # 1305 - # 1310 - - Tyr Gln Glu Phe Asp Glu Met Glu Glu Cys Al - #a Ser His Leu Pro Tyr 1315 - # 1320 - # 1325 - - Ile Glu Gln Gly Met Gln Leu Ala Glu Gln Ph - #e Lys Gln Lys Ala Leu 1330 - # 1335 - # 1340 - - Gly Leu Leu Gln Thr Ala Thr Lys Gln Ala Gl - #u Ala Ala Ala Pro Val 1345 1350 - # 1355 - # 1360 - - Val Glu Ser Lys Trp Arg Ala Leu Glu Thr Ph - #e Trp Ala Lys His Met 1365 - # 1370 - # 1375 - - Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu Al - #a Gly Leu Ser Thr Leu 1380 - # 1385 - # 1390 - - Pro Gly Asn Pro Ala Ile Ala Ser Leu Met Al - #a Phe Thr Ala Ser Ile 1395 - # 1400 - # 1405 - - Thr Ser Pro Leu Thr Thr Gln Ser Thr Leu Le - #u Phe Asn Ile Leu Gly 1410 - # 1415 - # 1420 - - Gly Trp Val Ala Ala Gln Leu Ala Pro Pro Se - #r Ala Ala Ser Ala Phe 1425 1430 - # 1435 - # 1440 - - Val Gly Ala Gly Ile Ala Gly Ala Ala Val Gl - #y Ser Ile Gly Leu Gly 1445 - # 1450 - # 1455 - - Lys Val Leu Val Asp Ile Leu Ala Gly Tyr Gl - #y Ala Gly Val Ala Gly 1460 - # 1465 - # 1470 - - Ala Leu Val Ala Phe Lys Val Met Ser Gly Gl - #u Met Pro Ser Thr Glu 1475 - # 1480 - # 1485 - - Asp Leu Val Asn Leu Leu Pro Ala Ile Leu Se - #r Pro Gly Ala Leu Val 1490 - # 1495 - # 1500 - - Val Gly Val Val Cys Ala Ala Ile Leu Arg Ar - #g His Val Gly Pro Gly 1505 1510 - # 1515 - # 1520 - - Glu Gly Ala Val Gln Trp Met Asn Arg Leu Il - #e Ala Phe Ala Ser Arg 1525 - # 1530 - # 1535 - - Gly Asn His Val Ser Pro Thr His Tyr Val Pr - #o Glu Ser Asp Ala Ala 1540 - # 1545 - # 1550 - - Ala Arg Val Thr Gln Ile Leu Ser Ser Leu Th - #r Ile Thr Gln Leu Leu 1555 - # 1560 - # 1565 - - Lys Arg Leu His Gln Trp Ile Asn Glu Asp Cy - #s Ser Thr Pro Cys Ser 1570 - # 1575 - # 1580 - - Gly Ser Trp Leu Arg Asp Val Trp Asp Trp Il - #e Cys Thr Val Leu Thr 1585 1590 - # 1595 - # 1600 - - Asp Phe Lys Thr Trp Leu Gln Ser Lys Leu Le - #u Pro Gln Leu Pro Gly 1605 - # 1610 - # 1615 - - Val Pro Phe Phe Ser Cys Gln Arg Gly Tyr Ly - #s Gly Val Trp Arg Gly 1620 - # 1625 - # 1630 - - Asp Gly Ile Met Gln Thr Thr Cys Pro Cys Gl - #y Ala Gln Ile Thr Gly 1635 - # 1640 - # 1645 - - His Val Lys Asn Gly Ser Met Arg Ile Val Gl - #y Pro Lys Thr Cys Ser 1650 - # 1655 - # 1660 - - Asn Thr Trp His Gly Thr Phe Pro Ile Asn Al - #a Tyr Thr Thr Gly Pro 1665 1670 - # 1675 - # 1680 - - Cys Thr Pro Ser Pro Ala Pro Asn Tyr Ser Ar - #g Ala Leu Trp Arg Val 1685 - # 1690 - # 1695 - - Ala Ala Glu Glu Tyr Val Glu Val Thr Arg Va - #l Gly Asp Phe His Tyr 1700 - # 1705 - # 1710 - - Val Thr Gly Met Thr Thr Asp Asn Val Lys Cy - #s Pro Cys Gln Val Pro 1715 - # 1720 - # 1725 - - Ala Pro Glu Phe Phe Ser Glu Val Asp Gly Va - #l Arg Leu His Arg Tyr 1730 - # 1735 - # 1740 - - Ala Pro Ala Cys Arg Pro Leu Leu Arg Glu Gl - #u Val Thr Phe Gln Val 1745 1750 - # 1755 - # 1760 - - Gly Leu Asn Gln Tyr Leu Val Gly Ser Gln Le - #u Pro Cys Glu Pro Glu 1765 - # 1770 - # 1775 - - Pro Asp Val Ala Val Leu Thr Ser Met Leu Th - #r Asp Pro Ser His Ile 1780 - # 1785 - # 1790 - - Thr Ala Glu Thr Ala Lys Arg Arg Leu Ala Ar - #g Gly Ser Pro Pro Ser 1795 - # 1800 - # 1805 - - Leu Ala Ser Ser Ser Ala Ser Gln Leu Ser Al - #a Pro Ser Leu Lys Ala 1810 - # 1815 - # 1820 - - Thr Cys Thr Thr His His Val Ser Pro Asp Al - #a Asp Leu Ile Glu Ala 1825 1830 - # 1835 - # 1840 - - Asn Leu Leu Trp Arg Gln Glu Met Gly Gly As - #n Ile Thr Arg Val Glu 1845 - # 1850 - # 1855 - - Ser Glu Asn Lys Val Val Val Leu Asp Ser Ph - #e Asp Pro Leu Arg Ala 1860 - # 1865 - # 1870 - - Glu Glu Asp Glu Arg Glu Val Ser Val Pro Al - #a Glu Ile Leu Arg Lys 1875 - # 1880 - # 1885 - - Ser Lys Lys Phe Pro Ala Ala Met Pro Ile Tr - #p Ala Arg Pro Asp Tyr 1890 - # 1895 - # 1900 - - Asn Pro Pro Leu Leu Glu Ser Trp Lys Asp Pr - #o Asp Tyr Val Pro Pro 1905 1910 - # 1915 - # 1920 - - Val Val His Gly Cys Pro Leu Pro Pro Ile Ly - #s Ala Pro Pro Ile Pro 1925 - # 1930 - # 1935 - - Pro Pro Arg Arg Lys Arg Thr Val Val Leu Th - #r Glu Ser Ser Val Ser 1940 - # 1945 - # 1950 - - Ser Ala Leu Ala Glu Leu Ala Thr Lys Thr Ph - #e Gly Ser Ser Glu Ser 1955 - # 1960 - # 1965 - - Ser Ala Val Asp Ser Gly Thr Ala Thr Ala Le - #u Pro Asp Gln Ala Ser 1970 - # 1975 - # 1980 - - Asp Asp Gly Asp Lys Gly Ser Asp Val Glu Se - #r Tyr Ser Ser Met Pro 1985 1990 - # 1995 - # 2000 - - Pro Leu Glu Gly Glu Pro Gly Asp Pro Asp Le - #u Ser Asp Gly Ser Trp 2005 - # 2010 - # 2015 - - Ser Thr Val Ser Glu Glu Ala Ser Glu Asp Va - #l Val Cys Cys Ser Met 2020 - # 2025 - # 2030 - - Ser Tyr Thr Trp Thr Gly Ala Leu Ile Thr Pr - #o Cys Ala Ala Glu Glu 2035 - # 2040 - # 2045 - - Ser Lys Leu Pro Ile Asn Ala Leu Ser Asn Se - #r Leu Leu Arg His His 2050 - # 2055 - # 2060 - - Asn Met Val Tyr Ala Thr Thr Ser Arg Ser Al - #a Gly Leu Arg Gln Lys 2065 2070 - # 2075 - # 2080 - - Lys Val Thr Phe Asp Arg Leu Gln Val Leu As - #p Asp His Tyr Arg Asp 2085 - # 2090 - # 2095 - - Val Leu Lys Glu Met Lys Ala Lys Ala Ser Th - #r Val Lys Ala Lys Leu 2100 - # 2105 - # 2110 - - Leu Ser Val Glu Glu Ala Cys Lys Leu Thr Pr - #o Pro His Ser Ala Lys 2115 - # 2120 - # 2125 - - Ser Lys Phe Gly Tyr Gly Ala Lys Asp Val Ar - #g Asn Leu Ser Ser Lys 2130 - # 2135 - # 2140 - - Ala Val Asn His Ile His Ser Val Trp Lys As - #p Leu Leu Glu Asp Thr 2145 2150 - # 2155 - # 2160 - - Val Thr Pro Ile Asp Thr Thr Ile Met Ala Ly - #s Asn Glu Val Phe Cys 2165 - # 2170 - # 2175 - - Val Gln Pro Glu Lys Gly Gly Arg Lys Pro Al - #a Arg Leu Ile Val Phe 2180 - # 2185 - # 2190 - - Pro Asp Leu Gly Val Arg Val Cys Glu Lys Me - #t Ala Leu Tyr Asp Val 2195 - # 2200 - # 2205 - - Val Ser Thr Leu Pro Gln Val Val Met Gly Se - #r Ser Tyr Gly Phe Gln 2210 - # 2215 - # 2220 - - Tyr Ser Pro Gly Gln Arg Val Glu Phe Leu Va - #l Asn Thr Trp Lys Ser 2225 2230 - # 2235 - # 2240 - - Lys Lys Asn Pro Met Gly Phe Ser Tyr Asp Th - #r Arg Cys Phe Asp Ser 2245 - # 2250 - # 2255 - - Thr Val Thr Glu Asn Asp Ile Arg Val Glu Gl - #u Ser Ile Tyr Gln Cys 2260 - # 2265 - # 2270 - - Cys Asp Leu Ala Pro Glu Ala Arg Gln Ala Il - #e Lys Ser Leu Thr Glu 2275 - # 2280 - # 2285 - - Arg Leu Tyr Ile Gly Gly Pro Leu Thr Asn Se - #r Lys Gly Gln Asn Cys 2290 - # 2295 - # 2300 - - Gly Tyr Arg Arg Cys Arg Ala Ser Gly Val Le - #u Thr Thr Ser Cys Gly 2305 2310 - # 2315 - # 2320 - - Asn Thr Leu Thr Cys Tyr Leu Lys Ala Ser Al - #a Ala Cys Arg Ala Ala 2325 - # 2330 - # 2335 - - Lys Leu Gln Asp Cys Thr Met Leu Val Asn Gl - #y Asp Asp Leu Val Val 2340 - # 2345 - # 2350 - - Ile Cys Glu Ser Ala Gly Thr Gln Glu Asp Al - #a Ala Ser Leu Arg Val 2355 - # 2360 - # 2365 - - Phe Thr Glu Ala Met Thr Arg Tyr Ser Ala Pr - #o Pro Gly Asp Pro Pro 2370 - # 2375 - # 2380 - - Gln Pro Glu Tyr Asp Leu Glu Leu Ile Thr Se - #r Cys Ser Ser Asn Val 2385 2390 - # 2395 - # 2400 - - Ser Val Ala His Asp Ala Ser Gly Lys Arg Va - #l Tyr Tyr Leu Thr Arg 2405 - # 2410 - # 2415 - - Asp Pro Thr Thr Pro Leu Ala Arg Ala Ala Tr - #p Glu Thr Ala Arg His 2420 - # 2425 - # 2430 - - Thr Pro Val Asn Ser Trp Leu Gly Asn Ile Il - #e Met Tyr Ala Pro Thr 2435 - # 2440 - # 2445 - - Leu Trp Ala Arg Met Ile Leu Met Thr His Ph - #e Phe Ser Ile Leu Leu 2450 - # 2455 - # 2460 - - Ala Gln Glu Gln Leu Glu Lys Ala Leu Asp Cy - #s Gln Ile Tyr Gly Ala 2465 2470 - # 2475 - # 2480 - - Cys Tyr Ser Ile Glu Pro Leu Asp Leu Pro Gl - #n Ile Ile Glu Arg Leu 2485 - # 2490 - # 2495 - - His Gly Leu Ser Ala Phe Ser Leu His Ser Ty - #r Ser Pro Gly Glu Ile 2500 - # 2505 - # 2510 - - Asn Arg Val Ala Ser Cys Leu Arg Lys Leu Gl - #y Val Pro Pro Leu Arg 2515 - # 2520 - # 2525 - - Val Trp Arg His Arg Ala Arg Ser Val Arg Al - #a Arg Leu Leu Ser Gln 2530 - # 2535 - # 2540 - - Gly Gly Arg Ala Ala Thr Cys Gly Lys Tyr Le - #u Phe Asn Trp Ala Val 2545 2550 - # 2555 - # 2560 - - Lys Thr Lys Leu Lys Leu Thr Pro Ile Pro Al - #a Ala Ser Arg Leu Asp 2565 - # 2570 - # 2575 - - Leu Ser Gly Trp Phe Val Ala Gly Tyr Ser Gl - #y Gly Asp Ile Tyr His 2580 - # 2585 - # 2590 - - Ser Leu Ser Arg Ala Arg Pro Arg Trp Phe Me - #t Leu Cys Leu Leu Leu 2595 - # 2600 - # 2605 - - Leu Ser Val Gly Val Gly Ile Tyr Leu Leu Pr - #o Asn Arg 2610 - # 2615 - # 2620 - - - - (2) INFORMATION FOR SEQ ID NO:37: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 831 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..831 (D) OTHER INFORMATION: - #/note: "sequence = 2520 - 3350 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..831 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:37: - - CGT GTC TGT GCC TGC TTG TGG ATG ATG CTG CT - #G ATA GCC CAG GCC GAG 48 Arg Val Cys Ala Cys Leu Trp Met Met Leu Le - #u Ile Ala Gln Ala Glu 1 5 - # 10 - # 15 - - GCC GCC TTG GAG AAC CTG GTG GTC CTC AAT TC - #G GCG TCT GTG GCC GGC 96 Ala Ala Leu Glu Asn Leu Val Val Leu Asn Se - #r Ala Ser Val Ala Gly 20 - # 25 - # 30 - - GCA CAT GGC ATC CTC TCC TTC CTT GTG TTC TT - #C TGT GCC GCC TGG TAC 144 Ala His Gly Ile Leu Ser Phe Leu Val Phe Ph - #e Cys Ala Ala Trp Tyr 35 - # 40 - # 45 - - ATC AAA GGC AGG CTG GTC CCT GGG GCG ACA TA - #T GCT CTT TAT GGC GTG 192 Ile Lys Gly Arg Leu Val Pro Gly Ala Thr Ty - #r Ala Leu Tyr Gly Val 50 - # 55 - # 60 - - TGG CCG CTG CTC CTG CTC TTG CTG GCA TTA CC - #A CCG CGA GCT TAC GCC 240 Trp Pro Leu Leu Leu Leu Leu Leu Ala Leu Pr - #o Pro Arg Ala Tyr Ala 65 - # 70 - # 75 - # 80 - - ATG GAC CGG GAG ATG GCT GCA TCG TGC GGA GG - #C GCG GTT TTT GTG GGT 288 Met Asp Arg Glu Met Ala Ala Ser Cys Gly Gl - #y Ala Val Phe Val Gly 85 - # 90 - # 95 - - CTG GTA CTC CTG ACT TTG TCA CCA TAC TAC AA - #G GTG TTC CTC GCT AGG 336 Leu Val Leu Leu Thr Leu Ser Pro Tyr Tyr Ly - #s Val Phe Leu Ala Arg 100 - # 105 - # 110 - - CTC ATA TGG TGG TTA CAA TAT TTT ACC ACC AG - #A GCC GAG GCG GAC TTA 384 Leu Ile Trp Trp Leu Gln Tyr Phe Thr Thr Ar - #g Ala Glu Ala Asp Leu 115 - # 120 - # 125 - - CAT GTG TGG ATC CCC CCC CTC AAC GCT CGG GG - #A GGC CGC GAT GCC ATC 432 His Val Trp Ile Pro Pro Leu Asn Ala Arg Gl - #y Gly Arg Asp Ala Ile 130 - # 135 - # 140 - - ATC CTC CTC ATG TGC GCA GTC CAT CCA GAG CT - #A ATC TTT GAC ATC ACC 480 Ile Leu Leu Met Cys Ala Val His Pro Glu Le - #u Ile Phe Asp Ile Thr 145 1 - #50 1 - #55 1 -#60 - - AAA CTT CTA ATT GCC ATA CTC GGT CCG CTC AT - #G GTG CTC CAA GCTGGC 528 Lys Leu Leu Ile Ala Ile Leu Gly Pro Leu Me - #t Val Leu Gln Ala Gly 165 - # 170 - # 175 - - ATA ACC AGA GTG CCG TAC TTC GTG CGC GCT CA - #A GGG CTC ATT CAT GCA 576 Ile Thr Arg Val Pro Tyr Phe Val Arg Ala Gl - #n Gly Leu Ile His Ala 180 - # 185 - # 190 - - TGC ATG TTA GTG CGG AAG GTC GCT GGG GGT CA - #T TAT GTC CAA ATG GCC 624 Cys Met Leu Val Arg Lys Val Ala Gly Gly Hi - #s Tyr Val Gln Met Ala 195 - # 200 - # 205 - - TTC ATG AAG CTG GGC GCG CTG ACA GGC ACG TA - #C ATT TAC AAC CAT CTT 672 Phe Met Lys Leu Gly Ala Leu Thr Gly Thr Ty - #r Ile Tyr Asn His Leu 210 - # 215 - # 220 - - ACC CCG CTA CGG GAT TGG CCA CGC GCG GGC CT - #A CGA GAC CTT GCG GTG 720 Thr Pro Leu Arg Asp Trp Pro Arg Ala Gly Le - #u Arg Asp Leu Ala Val 225 2 - #30 2 - #35 2 -#40 - - GCA GTG GAG CCC GTC GTC TTC TCC GAC ATG GA - #G ACC AAG ATC ATCACC 768 Ala Val Glu Pro Val Val Phe Ser Asp Met Gl - #u Thr Lys Ile Ile Thr 245 - # 250 - # 255 - - TGG GGA GCA GAC ACC GCG GCG TGT GGG GAC AT - #C ATC TTG GGT CTG CCC 816 Trp Gly Ala Asp Thr Ala Ala Cys Gly Asp Il - #e Ile Leu Gly Leu Pro 260 - # 265 - # 270 - - GTC TCC GCC CGA AGG - # - # - # 831 Val Ser Ala Arg Arg 275 - - - - (2) INFORMATION FOR SEQ ID NO:38: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 277 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:38: - - Arg Val Cys Ala Cys Leu Trp Met Met Leu Le - #u Ile Ala Gln Ala Glu 1 5 - # 10 - # 15 - - Ala Ala Leu Glu Asn Leu Val Val Leu Asn Se - #r Ala Ser Val Ala Gly 20 - # 25 - # 30 - - Ala His Gly Ile Leu Ser Phe Leu Val Phe Ph - #e Cys Ala Ala Trp Tyr 35 - # 40 - # 45 - - Ile Lys Gly Arg Leu Val Pro Gly Ala Thr Ty - #r Ala Leu Tyr Gly Val 50 - # 55 - # 60 - - Trp Pro Leu Leu Leu Leu Leu Leu Ala Leu Pr - #o Pro Arg Ala Tyr Ala 65 - # 70 - # 75 - # 80 - - Met Asp Arg Glu Met Ala Ala Ser Cys Gly Gl - #y Ala Val Phe Val Gly 85 - # 90 - # 95 - - Leu Val Leu Leu Thr Leu Ser Pro Tyr Tyr Ly - #s Val Phe Leu Ala Arg 100 - # 105 - # 110 - - Leu Ile Trp Trp Leu Gln Tyr Phe Thr Thr Ar - #g Ala Glu Ala Asp Leu 115 - # 120 - # 125 - - His Val Trp Ile Pro Pro Leu Asn Ala Arg Gl - #y Gly Arg Asp Ala Ile 130 - # 135 - # 140 - - Ile Leu Leu Met Cys Ala Val His Pro Glu Le - #u Ile Phe Asp Ile Thr 145 1 - #50 1 - #55 1 -#60 - - Lys Leu Leu Ile Ala Ile Leu Gly Pro Leu Me - #t Val Leu Gln AlaGly 165 - # 170 - # 175 - - Ile Thr Arg Val Pro Tyr Phe Val Arg Ala Gl - #n Gly Leu Ile His Ala 180 - # 185 - # 190 - - Cys Met Leu Val Arg Lys Val Ala Gly Gly Hi - #s Tyr Val Gln Met Ala 195 - # 200 - # 205 - - Phe Met Lys Leu Gly Ala Leu Thr Gly Thr Ty - #r Ile Tyr Asn His Leu 210 - # 215 - # 220 - - Thr Pro Leu Arg Asp Trp Pro Arg Ala Gly Le - #u Arg Asp Leu Ala Val 225 2 - #30 2 - #35 2 -#40 - - Ala Val Glu Pro Val Val Phe Ser Asp Met Gl - #u Thr Lys Ile IleThr 245 - # 250 - # 255 - - Trp Gly Ala Asp Thr Ala Ala Cys Gly Asp Il - #e Ile Leu Gly Leu Pro 260 - # 265 - # 270 - - Val Ser Ala Arg Arg 275 - - - - (2) INFORMATION FOR SEQ ID NO:39: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1827 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..1827 (D) OTHER INFORMATION: - #/note: "sequence = 3351 - 5177 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..1827 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:39: - - GGA AAG GAG ATA CTC CTG GGC CCG GCC GAT AG - #T CTT GAA GGG CGG GGG 48 Gly Lys Glu Ile Leu Leu Gly Pro Ala Asp Se - #r Leu Glu Gly Arg Gly 1 5 - # 10 - # 15 - - TTG CGA CTC CTC GCG CCC ATC ACG GCC TAC TC - #C CAA CAG ACG CGG GGC 96 Leu Arg Leu Leu Ala Pro Ile Thr Ala Tyr Se - #r Gln Gln Thr Arg Gly 20 - # 25 - # 30 - - CTA CTT GGT TGC ATC ATC ACT AGC CTT ACA GG - #C CGG GAC AAG AAC CAG 144 Leu Leu Gly Cys Ile Ile Thr Ser Leu Thr Gl - #y Arg Asp Lys Asn Gln 35 - # 40 - # 45 - - GTC GAG GGA GAG GTT CAG GTG GTT TCC ACC GC - #A ACA CAA TCC TTC CTG 192 Val Glu Gly Glu Val Gln Val Val Ser Thr Al - #a Thr Gln Ser Phe Leu 50 - # 55 - # 60 - - GCG ACC TGC GTC AAC GGC GTG TGT TGG ACC GT - #T TAC CAT GGT GCT GGC 240 Ala Thr Cys Val Asn Gly Val Cys Trp Thr Va - #l Tyr His Gly Ala Gly 65 - # 70 - # 75 - # 80 - - TCA AAG ACC TTA GCC GCG CCA AAG GGG CCA AT - #C ACC CAG ATG TAC ACT 288 Ser Lys Thr Leu Ala Ala Pro Lys Gly Pro Il - #e Thr Gln Met Tyr Thr 85 - # 90 - # 95 - - AAT GTG GAC CAG GAC CTC GTC GGC TGG CCC AA - #G CCC CCC GGG GCG CGT 336 Asn Val Asp Gln Asp Leu Val Gly Trp Pro Ly - #s Pro Pro Gly Ala Arg 100 - # 105 - # 110 - - TCC TTG ACA CCA TGC ACC TGT GGC AGC TCA GA - #C CTT TAC TTG GTC ACG 384 Ser Leu Thr Pro Cys Thr Cys Gly Ser Ser As - #p Leu Tyr Leu Val Thr 115 - # 120 - # 125 - - AGA CAT GCT GAC GTC ATT CCG GTG CGC CGG CG - #G GGC GAC AGT AGG GGG 432 Arg His Ala Asp Val Ile Pro Val Arg Arg Ar - #g Gly Asp Ser Arg Gly 130 - # 135 - # 140 - - AGC CTG CTC TCC CCC AGG CCT GTC TCC TAC TT - #G AAG GGC TCT TCG GGT 480 Ser Leu Leu Ser Pro Arg Pro Val Ser Tyr Le - #u Lys Gly Ser Ser Gly 145 1 - #50 1 - #55 1 -#60 - - GGT CCA CTG CTC TGC CCC TTC GGG CAC GCT GT - #G GGC ATC TTC CGGGCT 528 Gly Pro Leu Leu Cys Pro Phe Gly His Ala Va - #l Gly Ile Phe Arg Ala 165 - # 170 - # 175 - - GCC GTA TGC ACC CGG GGG GTT GCG AAG GCG GT - #G GAC TTT GTG CCC GTA 576 Ala Val Cys Thr Arg Gly Val Ala Lys Ala Va - #l Asp Phe Val Pro Val 180 - # 185 - # 190 - - GAG TCC ATG GAA ACT ACT ATG CGG TCT CCG GT - #C TTC ACG GAC AAC TCA 624 Glu Ser Met Glu Thr Thr Met Arg Ser Pro Va - #l Phe Thr Asp Asn Ser 195 - # 200 - # 205 - - TCC CCC CCG GCC GTA CCG CAG TCA TTT CAA GT - #G GCC CAC CTA CAC GCT 672 Ser Pro Pro Ala Val Pro Gln Ser Phe Gln Va - #l Ala His Leu His Ala 210 - # 215 - # 220 - - CCC ACT GGC AGC GGC AAG AGT ACT AAA GTG CC - #G GCT GCA TAT GCA GCC 720 Pro Thr Gly Ser Gly Lys Ser Thr Lys Val Pr - #o Ala Ala Tyr Ala Ala 225 2 - #30 2 - #35 2 -#40 - - CAA GGG TAC AAG GTG CTC GTC CTC AAT CCG TC - #C GTT GCC GCT ACCTTA 768 Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Se - #r Val Ala Ala Thr Leu 245 - # 250 - # 255 - - GGG TTT GGG GCG TAT ATG TCT AAG GCA CAC GG - #T ATT GAC CCC AAC ATC 816 Gly Phe Gly Ala Tyr Met Ser Lys Ala His Gl - #y Ile Asp Pro Asn Ile 260 - # 265 - # 270 - - AGA ACT GGG GTA AGG ACC ATT ACC ACA GGC GC - #C CCC GTC ACA TAC TCT 864 Arg Thr Gly Val Arg Thr Ile Thr Thr Gly Al - #a Pro Val Thr Tyr Ser 275 - # 280 - # 285 - - ACC TAT GGC AAG TTT CTT GCC GAT GGT GGT TG - #C TCT GGG GGC GCT TAT 912 Thr Tyr Gly Lys Phe Leu Ala Asp Gly Gly Cy - #s Ser Gly Gly Ala Tyr 290 - # 295 - # 300 - - GAC ATC ATA ATA TGT GAT GAG TGC CAT TCA AC - #T GAC TCG ACT ACA ATC 960 Asp Ile Ile Ile Cys Asp Glu Cys His Ser Th - #r Asp Ser Thr Thr Ile 305 3 - #10 3 - #15 3 -#20 - - TTG GGC ATC GGC ACA GTC CTG GAC CAA GCG GA - #G ACG GCT GGA GCGCGG 1008 Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Gl - #u Thr Ala Gly Ala Arg 325 - # 330 - # 335 - - CTT GTC GTG CTC GCC ACC GCT ACG CCT CCG GG - #A TCG GTC ACC GTG CCA 1056 Leu Val Val Leu Ala Thr Ala Thr Pro Pro Gl - #y Ser Val Thr Val Pro 340 - # 345 - # 350 - - CAC CCA AAC ATC GAG GAG GTG GCC CTG TCT AA - #T ACT GGA GAG ATC CCC 1104 His Pro Asn Ile Glu Glu Val Ala Leu Ser As - #n Thr Gly Glu Ile Pro 355 - # 360 - # 365 - - TTC TAT GGC AAA GCC ATC CCC ATT GAA GCC AT - #C AGG GGG GGA AGG CAT 1152 Phe Tyr Gly Lys Ala Ile Pro Ile Glu Ala Il - #e Arg Gly Gly Arg His 370 - # 375 - # 380 - - CTC ATT TTC TGT CAT TCC AAG AAG AAG TGC GA - #C GAG CTC GCC GCA AAG 1200 Leu Ile Phe Cys His Ser Lys Lys Lys Cys As - #p Glu Leu Ala Ala Lys 385 3 - #90 3 - #95 4 -#00 - - CTG TCA GGC CTC GGA ATC AAC GCT GTG GCG TA - #T TAC CGG GGG CTCGAT 1248 Leu Ser Gly Leu Gly Ile Asn Ala Val Ala Ty - #r Tyr Arg Gly Leu Asp 405 - # 410 - # 415 - - GTG TCC GTC ATA CCA ACT ATC GGA GAC GTC GT - #T GTC GTG GCA ACA GAC 1296 Val Ser Val Ile Pro Thr Ile Gly Asp Val Va - #l Val Val Ala Thr Asp 420 - # 425 - # 430 - - GCT CTG ATG ACG GGC TAT ACG GGC GAC TTT GA - #C TCA GTG ATC GAC TGT 1344 Ala Leu Met Thr Gly Tyr Thr Gly Asp Phe As - #p Ser Val Ile Asp Cys 435 - # 440 - # 445 - - AAC ACA TGT GTC ACC CAG ACA GTC GAC TTC AG - #C TTG GAT CCC ACC TTC 1392 Asn Thr Cys Val Thr Gln Thr Val Asp Phe Se - #r Leu Asp Pro Thr Phe 450 - # 455 - # 460 - - ACC ATT GAG ACG ACG ACC GTG CCT CAA GAC GC - #A GTG TCG CGC TCG CAG 1440 Thr Ile Glu Thr Thr Thr Val Pro Gln Asp Al - #a Val Ser Arg Ser Gln 465 4 - #70 4 - #75 4 -#80 - - CGG CGG GGT AGG ACT GGC AGG GGT AGG AGA GG - #C ATC TAC AGG TTTGTG 1488 Arg Arg Gly Arg Thr Gly Arg Gly Arg Arg Gl - #y Ile Tyr Arg Phe Val 485 - # 490 - # 495 - - ACT CCG GGA GAA CGG CCC TCG GGC ATG TTC GA - #T TCC TCG GTC CTG TGT 1536 Thr Pro Gly Glu Arg Pro Ser Gly Met Phe As - #p Ser Ser Val Leu Cys 500 - # 505 - # 510 - - GAG TGC TAT GAC GCG GGC TGT GCT TGG TAC GA - #G CTC ACC CCG GCC GAG 1584 Glu Cys Tyr Asp Ala Gly Cys Ala Trp Tyr Gl - #u Leu Thr Pro Ala Glu 515 - # 520 - # 525 - - ACC TCG GTT AGG TTG CGG GCC TAC CTG AAC AC - #A CCA GGG TTG CCC GTT 1632 Thr Ser Val Arg Leu Arg Ala Tyr Leu Asn Th - #r Pro Gly Leu Pro Val 530 - # 535 - # 540 - - TGC CAG GAC CAC CTG GAG TTC TGG GAG AGT GT - #C TTC ACA GGC CTC ACC 1680 Cys Gln Asp His Leu Glu Phe Trp Glu Ser Va - #l Phe Thr Gly Leu Thr 545 5 - #50 5 - #55 5 -#60 - - CAT ATA GAT GCA CAC TTC TTG TCC CAG ACC AA - #G CAG GCA GGA GACAAC 1728 His Ile Asp Ala His Phe Leu Ser Gln Thr Ly - #s Gln Ala Gly Asp Asn 565 - # 570 - # 575 - - TTC CCC TAC CTG GTA GCA TAC CAA GCC ACG GT - #G TGC GCC AGG GCT CAG 1776 Phe Pro Tyr Leu Val Ala Tyr Gln Ala Thr Va - #l Cys Ala Arg Ala Gln 580 - # 585 - # 590 - - GCC CCA CCT CCA TCA TGG GAT CAA ATG TGG AA - #G TGT CTC ATA CGG CTG 1824 Ala Pro Pro Pro Ser Trp Asp Gln Met Trp Ly - #s Cys Leu Ile Arg Leu 595 - # 600 - # 605 - - AAA - # - # - # 1827 Lys - - - - (2) INFORMATION FOR SEQ ID NO:40: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 609 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:40: - - Gly Lys Glu Ile Leu Leu Gly Pro Ala Asp Se - #r Leu Glu Gly Arg Gly 1 5 - # 10 - # 15 - - Leu Arg Leu Leu Ala Pro Ile Thr Ala Tyr Se - #r Gln Gln Thr Arg Gly 20 - # 25 - # 30 - - Leu Leu Gly Cys Ile Ile Thr Ser Leu Thr Gl - #y Arg Asp Lys Asn Gln 35 - # 40 - # 45 - - Val Glu Gly Glu Val Gln Val Val Ser Thr Al - #a Thr Gln Ser Phe Leu 50 - # 55 - # 60 - - Ala Thr Cys Val Asn Gly Val Cys Trp Thr Va - #l Tyr His Gly Ala Gly 65 - # 70 - # 75 - # 80 - - Ser Lys Thr Leu Ala Ala Pro Lys Gly Pro Il - #e Thr Gln Met Tyr Thr 85 - # 90 - # 95 - - Asn Val Asp Gln Asp Leu Val Gly Trp Pro Ly - #s Pro Pro Gly Ala Arg 100 - # 105 - # 110 - - Ser Leu Thr Pro Cys Thr Cys Gly Ser Ser As - #p Leu Tyr Leu Val Thr 115 - # 120 - # 125 - - Arg His Ala Asp Val Ile Pro Val Arg Arg Ar - #g Gly Asp Ser Arg Gly 130 - # 135 - # 140 - - Ser Leu Leu Ser Pro Arg Pro Val Ser Tyr Le - #u Lys Gly Ser Ser Gly 145 1 - #50 1 - #55 1 -#60 - - Gly Pro Leu Leu Cys Pro Phe Gly His Ala Va - #l Gly Ile Phe ArgAla 165 - # 170 - # 175 - - Ala Val Cys Thr Arg Gly Val Ala Lys Ala Va - #l Asp Phe Val Pro Val 180 - # 185 - # 190 - - Glu Ser Met Glu Thr Thr Met Arg Ser Pro Va - #l Phe Thr Asp Asn Ser 195 - # 200 - # 205 - - Ser Pro Pro Ala Val Pro Gln Ser Phe Gln Va - #l Ala His Leu His Ala 210 - # 215 - # 220 - - Pro Thr Gly Ser Gly Lys Ser Thr Lys Val Pr - #o Ala Ala Tyr Ala Ala 225 2 - #30 2 - #35 2 -#40 - - Gln Gly Tyr Lys Val Leu Val Leu Asn Pro Se - #r Val Ala Ala ThrLeu 245 - # 250 - # 255 - - Gly Phe Gly Ala Tyr Met Ser Lys Ala His Gl - #y Ile Asp Pro Asn Ile 260 - # 265 - # 270 - - Arg Thr Gly Val Arg Thr Ile Thr Thr Gly Al - #a Pro Val Thr Tyr Ser 275 - # 280 - # 285 - - Thr Tyr Gly Lys Phe Leu Ala Asp Gly Gly Cy - #s Ser Gly Gly Ala Tyr 290 - # 295 - # 300 - - Asp Ile Ile Ile Cys Asp Glu Cys His Ser Th - #r Asp Ser Thr Thr Ile 305 3 - #10 3 - #15 3 -#20 - - Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Gl - #u Thr Ala Gly AlaArg 325 - # 330 - # 335 - - Leu Val Val Leu Ala Thr Ala Thr Pro Pro Gl - #y Ser Val Thr Val Pro 340 - # 345 - # 350 - - His Pro Asn Ile Glu Glu Val Ala Leu Ser As - #n Thr Gly Glu Ile Pro 355 - # 360 - # 365 - - Phe Tyr Gly Lys Ala Ile Pro Ile Glu Ala Il - #e Arg Gly Gly Arg His 370 - # 375 - # 380 - - Leu Ile Phe Cys His Ser Lys Lys Lys Cys As - #p Glu Leu Ala Ala Lys 385 3 - #90 3 - #95 4 -#00 - - Leu Ser Gly Leu Gly Ile Asn Ala Val Ala Ty - #r Tyr Arg Gly LeuAsp 405 - # 410 - # 415 - - Val Ser Val Ile Pro Thr Ile Gly Asp Val Va - #l Val Val Ala Thr Asp 420 - # 425 - # 430 - - Ala Leu Met Thr Gly Tyr Thr Gly Asp Phe As - #p Ser Val Ile Asp Cys 435 - # 440 - # 445 - - Asn Thr Cys Val Thr Gln Thr Val Asp Phe Se - #r Leu Asp Pro Thr Phe 450 - # 455 - # 460 - - Thr Ile Glu Thr Thr Thr Val Pro Gln Asp Al - #a Val Ser Arg Ser Gln 465 4 - #70 4 - #75 4 -#80 - - Arg Arg Gly Arg Thr Gly Arg Gly Arg Arg Gl - #y Ile Tyr Arg PheVal 485 - # 490 - # 495 - - Thr Pro Gly Glu Arg Pro Ser Gly Met Phe As - #p Ser Ser Val Leu Cys 500 - # 505 - # 510 - - Glu Cys Tyr Asp Ala Gly Cys Ala Trp Tyr Gl - #u Leu Thr Pro Ala Glu 515 - # 520 - # 525 - - Thr Ser Val Arg Leu Arg Ala Tyr Leu Asn Th - #r Pro Gly Leu Pro Val 530 - # 535 - # 540 - - Cys Gln Asp His Leu Glu Phe Trp Glu Ser Va - #l Phe Thr Gly Leu Thr 545 5 - #50 5 - #55 5 -#60 - - His Ile Asp Ala His Phe Leu Ser Gln Thr Ly - #s Gln Ala Gly AspAsn 565 - # 570 - # 575 - - Phe Pro Tyr Leu Val Ala Tyr Gln Ala Thr Va - #l Cys Ala Arg Ala Gln 580 - # 585 - # 590 - - Ala Pro Pro Pro Ser Trp Asp Gln Met Trp Ly - #s Cys Leu Ile Arg Leu 595 - # 600 - # 605 - - Lys - - - - (2) INFORMATION FOR SEQ ID NO:41: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 90 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..90 (D) OTHER INFORMATION: - #/note: "sequence = 4485 - 4574 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..90 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:41: - - ATC AGG GGG GGA AGG CAT CTC ATT TTC TGT CA - #T TCC AAG AAG AAG TGC 48 Ile Arg Gly Gly Arg His Leu Ile Phe Cys Hi - #s Ser Lys Lys Lys Cys 1 5 - # 10 - # 15 - - GAC GAG CTC GCC GCA AAG CTG TCA GGC CTC GG - #A ATC AAC GCT - # 90 Asp Glu Leu Ala Ala Lys Leu Ser Gly Leu Gl - #y Ile Asn Ala 20 - # 25 - # 30 - - - - (2) INFORMATION FOR SEQ ID NO:42: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 30 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:42: - - Ile Arg Gly Gly Arg His Leu Ile Phe Cys Hi - #s Ser Lys Lys Lys Cys 1 5 - # 10 - # 15 - - Asp Glu Leu Ala Ala Lys Leu Ser Gly Leu Gl - #y Ile Asn Ala 20 - # 25 - # 30 - - - - (2) INFORMATION FOR SEQ ID NO:43: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 741 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..741 (D) OTHER INFORMATION: - #/note: "sequence = 5178 - 5918 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..741 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:43: - - CCT ACG CTG CAC GGG CCA ACA CCC TTG CTG TA - #C AGG CTG GGA GCC GTC 48 Pro Thr Leu His Gly Pro Thr Pro Leu Leu Ty - #r Arg Leu Gly Ala Val 1 5 - # 10 - # 15 - - CAG AAT GAG GTC ACC CTC ACC CAC CCC ATA AC - #C AAA TAC ATC ATG GCA 96 Gln Asn Glu Val Thr Leu Thr His Pro Ile Th - #r Lys Tyr Ile Met Ala 20 - # 25 - # 30 - - TGC ATG TCG GCT GAC CTG GAG GTC GTC ACT AG - #C ACC TGG GTG CTG GTG 144 Cys Met Ser Ala Asp Leu Glu Val Val Thr Se - #r Thr Trp Val Leu Val 35 - # 40 - # 45 - - GGC GGA GTC CTT GCA GCT CTG GCC GCG TAT TG - #C CTG ACA ACA GGC AGT 192 Gly Gly Val Leu Ala Ala Leu Ala Ala Tyr Cy - #s Leu Thr Thr Gly Ser 50 - # 55 - # 60 - - GTG GTC ATT GTG GGT AGG ATT ATC TTG TCC GG - #G AGG CCG GCC ATT GTT 240 Val Val Ile Val Gly Arg Ile Ile Leu Ser Gl - #y Arg Pro Ala Ile Val 65 - # 70 - # 75 - # 80 - - CCC GAC AGG GAG CTT CTC TAC CAG GAG TTC GA - #T GAA ATG GAA GAG TGC 288 Pro Asp Arg Glu Leu Leu Tyr Gln Glu Phe As - #p Glu Met Glu Glu Cys 85 - # 90 - # 95 - - GCC TCG CAC CTC CCT TAC ATC GAG CAG GGA AT - #G CAG CTC GCC GAG CAA 336 Ala Ser His Leu Pro Tyr Ile Glu Gln Gly Me - #t Gln Leu Ala Glu Gln 100 - # 105 - # 110 - - TTC AAG CAG AAA GCG CTC GGG TTA CTG CAA AC - #A GCC ACC AAA CAA GCG 384 Phe Lys Gln Lys Ala Leu Gly Leu Leu Gln Th - #r Ala Thr Lys Gln Ala 115 - # 120 - # 125 - - GAG GCT GCT GCT CCC GTG GTG GAG TCC AAG TG - #G CGA GCC CTT GAG ACA 432 Glu Ala Ala Ala Pro Val Val Glu Ser Lys Tr - #p Arg Ala Leu Glu Thr 130 - # 135 - # 140 - - TTC TGG GCG AAG CAC ATG TGG AAT TTC ATC AG - #C GGG ATA CAG TAC TTA 480 Phe Trp Ala Lys His Met Trp Asn Phe Ile Se - #r Gly Ile Gln Tyr Leu 145 1 - #50 1 - #55 1 -#60 - - GCA GGC TTA TCC ACT CTG CCT GGG AAC CCC GC - #A ATA GCA TCA TTGATG 528 Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Al - #a Ile Ala Ser Leu Met 165 - # 170 - # 175 - - GCA TTC ACA GCC TCT ATC ACC AGC CCG CTC AC - #C ACC CAA AGT ACC CTC 576 Ala Phe Thr Ala Ser Ile Thr Ser Pro Leu Th - #r Thr Gln Ser Thr Leu 180 - # 185 - # 190 - - CTG TTT AAC ATC TTG GGG GGG TGG GTG GCT GC - #C CAA CTC GCC CCC CCC 624 Leu Phe Asn Ile Leu Gly Gly Trp Val Ala Al - #a Gln Leu Ala Pro Pro 195 - # 200 - # 205 - - AGC GCC GCT TCG GCT TTC GTG GGC GCC GGC AT - #C GCC GGT GCG GCT GTT 672 Ser Ala Ala Ser Ala Phe Val Gly Ala Gly Il - #e Ala Gly Ala Ala Val 210 - # 215 - # 220 - - GGC AGC ATA GGC CTT GGG AAG GTG CTT GTG GA - #C ATT CTG GCG GGT TAT 720 Gly Ser Ile Gly Leu Gly Lys Val Leu Val As - #p Ile Leu Ala Gly Tyr 225 2 - #30 2 - #35 2 -#40 - - GGA GCA GGA GTG GCC GGC GCG - # - # 741 Gly Ala Gly Val Ala Gly Ala 245 - - - - (2) INFORMATION FOR SEQ ID NO:44: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 247 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:44: - - Pro Thr Leu His Gly Pro Thr Pro Leu Leu Ty - #r Arg Leu Gly Ala Val 1 5 - # 10 - # 15 - - Gln Asn Glu Val Thr Leu Thr His Pro Ile Th - #r Lys Tyr Ile Met Ala 20 - # 25 - # 30 - - Cys Met Ser Ala Asp Leu Glu Val Val Thr Se - #r Thr Trp Val Leu Val 35 - # 40 - # 45 - - Gly Gly Val Leu Ala Ala Leu Ala Ala Tyr Cy - #s Leu Thr Thr Gly Ser 50 - # 55 - # 60 - - Val Val Ile Val Gly Arg Ile Ile Leu Ser Gl - #y Arg Pro Ala Ile Val 65 - # 70 - # 75 - # 80 - - Pro Asp Arg Glu Leu Leu Tyr Gln Glu Phe As - #p Glu Met Glu Glu Cys 85 - # 90 - # 95 - - Ala Ser His Leu Pro Tyr Ile Glu Gln Gly Me - #t Gln Leu Ala Glu Gln 100 - # 105 - # 110 - - Phe Lys Gln Lys Ala Leu Gly Leu Leu Gln Th - #r Ala Thr Lys Gln Ala 115 - # 120 - # 125 - - Glu Ala Ala Ala Pro Val Val Glu Ser Lys Tr - #p Arg Ala Leu Glu Thr 130 - # 135 - # 140 - - Phe Trp Ala Lys His Met Trp Asn Phe Ile Se - #r Gly Ile Gln Tyr Leu 145 1 - #50 1 - #55 1 -#60 - - Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Al - #a Ile Ala Ser LeuMet 165 - # 170 - # 175 - - Ala Phe Thr Ala Ser Ile Thr Ser Pro Leu Th - #r Thr Gln Ser Thr Leu 180 - # 185 - # 190 - - Leu Phe Asn Ile Leu Gly Gly Trp Val Ala Al - #a Gln Leu Ala Pro Pro 195 - # 200 - # 205 - - Ser Ala Ala Ser Ala Phe Val Gly Ala Gly Il - #e Ala Gly Ala Ala Val 210 - # 215 - # 220 - - Gly Ser Ile Gly Leu Gly Lys Val Leu Val As - #p Ile Leu Ala Gly Tyr 225 2 - #30 2 - #35 2 -#40 - - Gly Ala Gly Val Ala Gly Ala 245 - - - - (2) INFORMATION FOR SEQ ID NO:45: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 90 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..90 (D) OTHER INFORMATION: - #/note: "sequence = 5544 - 5633 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..90 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:45: - - ACA GCC ACC AAA CAA GCG GAG GCT GCT GCT CC - #C GTG GTG GAG TCC AAG 48 Thr Ala Thr Lys Gln Ala Glu Ala Ala Ala Pr - #o Val Val Glu Ser Lys 1 5 - # 10 - # 15 - - TGG CGA GCC CTT GAG ACA TTC TGG GCG AAG CA - #C ATG TGG AAT - # 90 Trp Arg Ala Leu Glu Thr Phe Trp Ala Lys Hi - #s Met Trp Asn 20 - # 25 - # 30 - - - - (2) INFORMATION FOR SEQ ID NO:46: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 30 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:46: - - Thr Ala Thr Lys Gln Ala Glu Ala Ala Ala Pr - #o Val Val Glu Ser Lys 1 5 - # 10 - # 15 - - Trp Arg Ala Leu Glu Thr Phe Trp Ala Lys Hi - #s Met Trp Asn 20 - # 25 - # 30 - - - - (2) INFORMATION FOR SEQ ID NO:47: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 453 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..453 (D) OTHER INFORMATION: - #/note: "sequence = 5919 - 6371 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..453 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:47: - - CTC GTG GCC TTT AAG GTC ATG AGC GGC GAG AT - #G CCC TCC ACC GAG GAC 48 Leu Val Ala Phe Lys Val Met Ser Gly Glu Me - #t Pro Ser Thr Glu Asp 1 5 - # 10 - # 15 - - CTG GTC AAT CTA CTT CCT GCC ATC CTC TCT CC - #T GGC GCC CTG GTC GTC 96 Leu Val Asn Leu Leu Pro Ala Ile Leu Ser Pr - #o Gly Ala Leu Val Val 20 - # 25 - # 30 - - GGG GTC GTG TGT GCA GCA ATA CTG CGT CGA CA - #C GTG GGT CCG GGA GAG 144 Gly Val Val Cys Ala Ala Ile Leu Arg Arg Hi - #s Val Gly Pro Gly Glu 35 - # 40 - # 45 - - GGG GCT GTG CAG TGG ATG AAC CGG CTG ATA GC - #G TTC GCC TCG CGG GGT 192 Gly Ala Val Gln Trp Met Asn Arg Leu Ile Al - #a Phe Ala Ser Arg Gly 50 - # 55 - # 60 - - AAT CAT GTT TCC CCC ACG CAC TAT GTG CCT GA - #G AGC GAC GCC GCA GCG 240 Asn His Val Ser Pro Thr His Tyr Val Pro Gl - #u Ser Asp Ala Ala Ala 65 - # 70 - # 75 - # 80 - - CGT GTT ACT CAG ATC CTC TCC AGC CTT ACC AT - #C ACT CAG CTG CTG AAA 288 Arg Val Thr Gln Ile Leu Ser Ser Leu Thr Il - #e Thr Gln Leu Leu Lys 85 - # 90 - # 95 - - AGG CTC CAC CAG TGG ATT AAT GAA GAC TGC TC - #C ACA CCG TGT TCC GGC 336 Arg Leu His Gln Trp Ile Asn Glu Asp Cys Se - #r Thr Pro Cys Ser Gly 100 - # 105 - # 110 - - TCG TGG CTA AGG GAT GTT TGG GAC TGG ATA TG - #C ACG GTG TTG ACT GAC 384 Ser Trp Leu Arg Asp Val Trp Asp Trp Ile Cy - #s Thr Val Leu Thr Asp 115 - # 120 - # 125 - - TTC AAG ACC TGG CTC CAG TCC AAG CTC CTG CC - #G CAG CTA CCT GGA GTC 432 Phe Lys Thr Trp Leu Gln Ser Lys Leu Leu Pr - #o Gln Leu Pro Gly Val 130 - # 135 - # 140 - - CCT TTT TTC TCG TGC CAA CGC - # - # 453 Pro Phe Phe Ser Cys Gln Arg 145 1 - #50 - - - - (2) INFORMATION FOR SEQ ID NO:48: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 151 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:48: - - Leu Val Ala Phe Lys Val Met Ser Gly Glu Me - #t Pro Ser Thr Glu Asp 1 5 - # 10 - # 15 - - Leu Val Asn Leu Leu Pro Ala Ile Leu Ser Pr - #o Gly Ala Leu Val Val 20 - # 25 - # 30 - - Gly Val Val Cys Ala Ala Ile Leu Arg Arg Hi - #s Val Gly Pro Gly Glu 35 - # 40 - # 45 - - Gly Ala Val Gln Trp Met Asn Arg Leu Ile Al - #a Phe Ala Ser Arg Gly 50 - # 55 - # 60 - - Asn His Val Ser Pro Thr His Tyr Val Pro Gl - #u Ser Asp Ala Ala Ala 65 - # 70 - # 75 - # 80 - - Arg Val Thr Gln Ile Leu Ser Ser Leu Thr Il - #e Thr Gln Leu Leu Lys 85 - # 90 - # 95 - - Arg Leu His Gln Trp Ile Asn Glu Asp Cys Se - #r Thr Pro Cys Ser Gly 100 - # 105 - # 110 - - Ser Trp Leu Arg Asp Val Trp Asp Trp Ile Cy - #s Thr Val Leu Thr Asp 115 - # 120 - # 125 - - Phe Lys Thr Trp Leu Gln Ser Lys Leu Leu Pr - #o Gln Leu Pro Gly Val 130 - # 135 - # 140 - - Pro Phe Phe Ser Cys Gln Arg 145 1 - #50 - - - - (2) INFORMATION FOR SEQ ID NO:49: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2991 base - #pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: cDNA from genomic - #RNA - - (ix) FEATURE: (A) NAME/KEY: misc.sub.-- - #feature (B) LOCATION: 1..2991 (D) OTHER INFORMATION: - #/note: "sequence = 6372 - 9362 of SEQ ID - #NO: 1" - - (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..2991 - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:49: - - GGG TAC AAG GGA GTC TGG CGG GGA GAC GGC AT - #C ATG CAA ACC ACC TGC 48 Gly Tyr Lys Gly Val Trp Arg Gly Asp Gly Il - #e Met Gln Thr Thr Cys 1 5 - # 10 - # 15 - - CCA TGT GGA GCA CAG ATC ACC GGA CAT GTC AA - #A AAC GGT TCC ATG AGG 96 Pro Cys Gly Ala Gln Ile Thr Gly His Val Ly - #s Asn Gly Ser Met Arg 20 - # 25 - # 30 - - ATC GTC GGG CCT AAG ACC TGC AGC AAC ACG TG - #G CAT GGA ACA TTC CCC 144 Ile Val Gly Pro Lys Thr Cys Ser Asn Thr Tr - #p His Gly Thr Phe Pro 35 - # 40 - # 45 - - ATC AAC GCA TAC ACC ACG GGC CCC TGC ACA CC - #C TCT CCA GCG CCA AAC 192 Ile Asn Ala Tyr Thr Thr Gly Pro Cys Thr Pr - #o Ser Pro Ala Pro Asn 50 - # 55 - # 60 - - TAT TCT AGG GCG CTG TGG CGG GTG GCC GCT GA - #G GAG TAC GTG GAG GTC 240 Tyr Ser Arg Ala Leu Trp Arg Val Ala Ala Gl - #u Glu Tyr Val Glu Val 65 - # 70 - # 75 - # 80 - - ACG CGG GTG GGG GAT TTC CAC TAC GTG ACG GG - #C ATG ACC ACT GAC AAC 288 Thr Arg Val Gly Asp Phe His Tyr Val Thr Gl - #y Met Thr Thr Asp Asn 85 - # 90 - # 95 - - GTA AAG TGC CCA TGC CAG GTT CCG GCT CCT GA - #A TTC TTC TCG GAG GTG 336 Val Lys Cys Pro Cys Gln Val Pro Ala Pro Gl - #u Phe Phe Ser Glu Val 100 - # 105 - # 110 - - GAC GGA GTG CGG TTG CAC AGG TAC GCT CCG GC - #G TGC AGG CCT CTC CTA 384 Asp Gly Val Arg Leu His Arg Tyr Ala Pro Al - #a Cys Arg Pro Leu Leu 115 - # 120 - # 125 - - CGG GAG GAG GTT ACA TTC CAG GTC GGG CTC AA - #C CAA TAC CTG GTT GGG 432 Arg Glu Glu Val Thr Phe Gln Val Gly Leu As - #n Gln Tyr Leu Val Gly 130 - # 135 - # 140 - - TCA CAG CTA CCA TGC GAG CCC GAA CCG GAT GT - #A GCA GTG CTC ACT TCC 480 Ser Gln Leu Pro Cys Glu Pro Glu Pro Asp Va - #l Ala Val Leu Thr Ser 145 1 - #50 1 - #55 1 -#60 - - ATG CTC ACC GAC CCC TCC CAC ATC ACA GCA GA - #A ACG GCT AAG CGTAGG 528 Met Leu Thr Asp Pro Ser His Ile Thr Ala Gl - #u Thr Ala Lys Arg Arg 165 - # 170 - # 175 - - TTG GCC AGG GGG TCT CCC CCC TCC TTG GCC AG - #C TCT TCA GCT AGC CAG 576 Leu Ala Arg Gly Ser Pro Pro Ser Leu Ala Se - #r Ser Ser Ala Ser Gln 180 - # 185 - # 190 - - TTG TCT GCG CCT TCC TTG AAG GCG ACA TGC AC - #T ACC CAC CAT GTC TCT 624 Leu Ser Ala Pro Ser Leu Lys Ala Thr Cys Th - #r Thr His His Val Ser 195 - # 200 - # 205 - - CCG GAC GCT GAC CTC ATC GAG GCC AAC CTC CT - #G TGG CGG CAG GAG ATG 672 Pro Asp Ala Asp Leu Ile Glu Ala Asn Leu Le - #u Trp Arg Gln Glu Met 210 - # 215 - # 220 - - GGC GGG AAC ATC ACC CGC GTG GAG TCG GAG AA - #C AAG GTG GTA GTC CTG 720 Gly Gly Asn Ile Thr Arg Val Glu Ser Glu As - #n Lys Val Val Val Leu 225 2 - #30 2 - #35 2 -#40 - - GAC TCT TTC GAC CCG CTT CGA GCG GAG GAG GA - #T GAG AGG GAA GTATCC 768 Asp Ser Phe Asp Pro Leu Arg Ala Glu Glu As - #p Glu Arg Glu Val Ser 245 - # 250 - # 255 - - GTT CCG GCG GAG ATC CTG CGG AAA TCC AAG AA - #G TTC CCC GCA GCG ATG 816 Val Pro Ala Glu Ile Leu Arg Lys Ser Lys Ly - #s Phe Pro Ala Ala Met 260 - # 265 - # 270 - - CCC ATC TGG GCG CGC CCG GAT TAC AAC CCT CC - #A CTG TTA GAG TCC TGG 864 Pro Ile Trp Ala Arg Pro Asp Tyr Asn Pro Pr - #o Leu Leu Glu Ser Trp 275 - # 280 - # 285 - - AAG GAC CCG GAC TAC GTC CCT CCG GTG GTG CA - #C GGG TGC CCG TTG CCA 912 Lys Asp Pro Asp Tyr Val Pro Pro Val Val Hi - #s Gly Cys Pro Leu Pro 290 - # 295 - # 300 - - CCT ATC AAG GCC CCT CCA ATA CCA CCT CCA CG - #G AGA AAG AGG ACG GTT 960 Pro Ile Lys Ala Pro Pro Ile Pro Pro Pro Ar - #g Arg Lys Arg Thr Val 305 3 - #10 3 - #15 3 -#20 - - GTC CTA ACA GAG TCC TCC GTG TCT TCT GCC TT - #A GCG GAG CTC GCTACT 1008 Val Leu Thr Glu Ser Ser Val Ser Ser Ala Le - #u Ala Glu Leu Ala Thr 325 - # 330 - # 335 - - AAG ACC TTC GGC AGC TCC GAA TCA TCG GCC GT - #C GAC AGC GGC ACG GCG 1056 Lys Thr Phe Gly Ser Ser Glu Ser Ser Ala Va - #l Asp Ser Gly Thr Ala 340 - # 345 - # 350 - - ACC GCC CTT CCT GAC CAG GCC TCC GAC GAC GG - #T GAC AAA GGA TCC GAC 1104 Thr Ala Leu Pro Asp Gln Ala Ser Asp Asp Gl - #y Asp Lys Gly Ser Asp 355 - # 360 - # 365 - - GTT GAG TCG TAC TCC TCC ATG CCC CCC CTT GA - #G GGG GAA CCG GGG GAC 1152 Val Glu Ser Tyr Ser Ser Met Pro Pro Leu Gl - #u Gly Glu Pro Gly Asp 370 - # 375 - # 380 - - CCC GAT CTC AGT GAC GGG TCT TGG TCT ACC GT - #G AGC GAG GAA GCT AGT 1200 Pro Asp Leu Ser Asp Gly Ser Trp Ser Thr Va - #l Ser Glu Glu Ala Ser 385 3 - #90 3 - #95 4 -#00 - - GAG GAT GTC GTC TGC TGC TCA ATG TCC TAC AC - #A TGG ACA GGC GCCTTG 1248 Glu Asp Val Val Cys Cys Ser Met Ser Tyr Th - #r Trp Thr Gly Ala Leu 405 - # 410 - # 415 - - ATC ACG CCA TGC GCT GCG GAG GAA AGC AAG CT - #G CCC ATC AAC GCG TTG 1296 Ile Thr Pro Cys Ala Ala Glu Glu Ser Lys Le - #u Pro Ile Asn Ala Leu 420 - # 425 - # 430 - - AGC AAC TCT TTG CTG CGC CAC CAT AAC ATG GT - #T TAT GCC ACA ACA TCT 1344 Ser Asn Ser Leu Leu Arg His His Asn Met Va - #l Tyr Ala Thr Thr Ser 435 - # 440 - # 445 - - CGC AGC GCA GGC CTG CGG CAG AAG AAG GTC AC - #C TTT GAC AGA CTG CAA 1392 Arg Ser Ala Gly Leu Arg Gln Lys Lys Val Th - #r Phe Asp Arg Leu Gln 450 - # 455 - # 460 - - GTC CTG GAC GAC CAC TAC CGG GAC GTG CTC AA - #G GAG ATG AAG GCG AAG 1440 Val Leu Asp Asp His Tyr Arg Asp Val Leu Ly - #s Glu Met Lys Ala Lys 465 4 - #70 4 - #75 4 -#80 - - GCG TCC ACA GTT AAG GCT AAA CTC CTA TCC GT - #A GAG GAA GCC TGCAAG 1488 Ala Ser Thr Val Lys Ala Lys Leu Leu Ser Va - #l Glu Glu Ala Cys Lys 485 - # 490 - # 495 - - CTG ACG CCC CCA CAT TCG GCC AAA TCC AAG TT - #T GGC TAT GGG GCA AAG 1536 Leu Thr Pro Pro His Ser Ala Lys Ser Lys Ph - #e Gly Tyr Gly Ala Lys 500 - # 505 - # 510 - - GAC GTC CGG AAC CTA TCC AGC AAG GCC GTT AA - #C CAC ATC CAC TCC GTG 1584 Asp Val Arg Asn Leu Ser Ser Lys Ala Val As - #n His Ile His Ser Val 515 - # 520 - # 525 - - TGG AAG GAC TTG CTG GAA GAC ACT GTG ACA CC - #A ATT GAC ACC ACC ATC 1632 Trp Lys Asp Leu Leu Glu Asp Thr Val Thr Pr - #o Ile Asp Thr Thr Ile 530 - # 535 - # 540 - - ATG GCA AAA AAT GAG GTT TTC TGT GTC CAA CC - #A GAG AAA GGA GGC CGT 1680 Met Ala Lys Asn Glu Val Phe Cys Val Gln Pr - #o Glu Lys Gly Gly Arg 545 5 - #50 5 - #55 5 -#60 - - AAG CCA GCC CGC CTT ATC GTA TTC CCA GAT CT - #G GGA GTC CGT GTATGC 1728 Lys Pro Ala Arg Leu Ile Val Phe Pro Asp Le - #u Gly Val Arg Val Cys 565 - # 570 - # 575 - - GAG AAG ATG GCC CTC TAT GAT GTG GTC TCC AC - #C CTT CCT CAG GTC GTG 1776 Glu Lys Met Ala Leu Tyr Asp Val Val Ser Th - #r Leu Pro Gln Val Val 580 - # 585 - # 590 - - ATG GGC TCC TCA TAC GGA TTC CAG TAC TCT CC - #T GGG CAG CGA GTC GAG 1824 Met Gly Ser Ser Tyr Gly Phe Gln Tyr Ser Pr - #o Gly Gln Arg Val Glu 595 - # 600 - # 605 - - TTC CTG GTG AAT ACC TGG AAA TCA AAG AAA AA - #C CCC ATG GGC TTT TCA 1872 Phe Leu Val Asn Thr Trp Lys Ser Lys Lys As - #n Pro Met Gly Phe Ser 610 - # 615 - # 620 - - TAT GAC ACT CGC TGT TTC GAC TCA ACG GTC AC - #C GAG AAC GAC ATC CGT 1920 Tyr Asp Thr Arg Cys Phe Asp Ser Thr Val Th - #r Glu Asn Asp Ile Arg 625 6 - #30 6 - #35 6 -#40 - - GTT GAG GAG TCA ATT TAC CAA TGT TGT GAC TT - #G GCC CCC GAA GCCAGA 1968 Val Glu Glu Ser Ile Tyr Gln Cys Cys Asp Le - #u Ala Pro Glu Ala Arg 645 - # 650 - # 655 - - CAG GCC ATA AAA TCG CTC ACA GAG CGG CTT TA - #T ATC GGG GGT CCT CTG 2016 Gln Ala Ile Lys Ser Leu Thr Glu Arg Leu Ty - #r Ile Gly Gly Pro Leu 660 - # 665 - # 670 - - ACT AAT TCA AAA GGG CAG AAC TGC GGT TAT CG - #C CGG TGC CGC GCG AGC 2064 Thr Asn Ser Lys Gly Gln Asn Cys Gly Tyr Ar - #g Arg Cys Arg Ala Ser 675 - # 680 - # 685 - - GGC GTG CTG ACG ACT AGC TGC GGT AAC ACC CT - #C ACA TGT TAC TTG AAG 2112 Gly Val Leu Thr Thr Ser Cys Gly Asn Thr Le - #u Thr Cys Tyr Leu Lys 690 - # 695 - # 700 - - GCC TCT GCA GCC TGT CGA GCT GCG AAG CTC CA - #G GAC TGC ACG ATG CTC 2160 Ala Ser Ala Ala Cys Arg Ala Ala Lys Leu Gl - #n Asp Cys Thr Met Leu 705 7 - #10 7 - #15 7 -#20 - - GTG AAC GGA GAC GAC CTC GTC GTT ATC TGT GA - #A AGC GCG GGA ACCCAA 2208 Val Asn Gly Asp Asp Leu Val Val Ile Cys Gl - #u Ser Ala Gly Thr Gln 725 - # 730 - # 735 - - GAG GAC GCG GCG AGC CTA CGA GTC TTC ACG GA - #G GCT ATG ACT AGG TAC 2256 Glu Asp Ala Ala Ser Leu Arg Val Phe Thr Gl - #u Ala Met Thr Arg Tyr 740 - # 745 - # 750 - - TCC GCC CCC CCC GGG GAC CCG CCC CAA CCA GA - #A TAC GAC TTG GAG CTG 2304 Ser Ala Pro Pro Gly Asp Pro Pro Gln Pro Gl - #u Tyr Asp Leu Glu Leu 755 - # 760 - # 765 - - ATA ACA TCA TGT TCC TCC AAT GTG TCG GTC GC - #C CAC GAT GCA TCA GGC 2352 Ile Thr Ser Cys Ser Ser Asn Val Ser Val Al - #a His Asp Ala Ser Gly 770 - # 775 - # 780 - - AAA AGG GTG TAC TAC CTC ACC CGT GAT CCC AC - #C ACC CCC CTA GCA CGG 2400 Lys Arg Val Tyr Tyr Leu Thr Arg Asp Pro Th - #r Thr Pro Leu Ala Arg 785 7 - #90 7 - #95 8 -#00 - - GCT GCG TGG GAG ACA GCT AGA CAC ACT CCA GT - #T AAC TCC TGG CTAGGC 2448 Ala Ala Trp Glu Thr Ala Arg His Thr Pro Va - #l Asn Ser Trp Leu Gly 805 - # 810 - # 815 - - AAC ATT ATT ATG TAT GCG CCC ACT TTG TGG GC - #A AGG ATG ATT CTG ATG 2496 Asn Ile Ile Met Tyr Ala Pro Thr Leu Trp Al - #a Arg Met Ile Leu Met 820 - # 825 - # 830 - - ACT CAC TTC TTC TCC ATC CTT CTA GCG CAG GA - #G CAA CTT GAA AAA GCC 2544 Thr His Phe Phe Ser Ile Leu Leu Ala Gln Gl - #u Gln Leu Glu Lys Ala 835 - # 840 - # 845 - - CTG GAC TGC CAG ATC TAC GGG GCC TGT TAC TC - #C ATT GAG CCA CTT GAC 2592 Leu Asp Cys Gln Ile Tyr Gly Ala Cys Tyr Se - #r Ile Glu Pro Leu Asp 850 - # 855 - # 860 - - CTA CCT CAG ATC ATT GAA CGA CTC CAT GGC CT - #T AGC GCA TTT TCA CTC 2640 Leu Pro Gln Ile Ile Glu Arg Leu His Gly Le - #u Ser Ala Phe Ser Leu 865 8 - #70 8 - #75 8 -#80 - - CAT AGT TAC TCT CCA GGT GAG ATC AAT AGG GT - #G GCT TCA TGC CTCAGG 2688 His Ser Tyr Ser Pro Gly Glu Ile Asn Arg Va - #l Ala Ser Cys Leu Arg 885 - # 890 - # 895 - - AAA CTT GGG GTA CCA CCC TTG CGA GTC TGG AG - #A CAT CGG GCC AGG AGC 2736 Lys Leu Gly Val Pro Pro Leu Arg Val Trp Ar - #g His Arg Ala Arg Ser 900 - # 905 - # 910 - - GTC CGC GCT AGG CTA CTG TCC CAG GGA GGG AG - #G GCC GCC ACT TGT GGC 2784 Val Arg Ala Arg Leu Leu Ser Gln Gly Gly Ar - #g Ala Ala Thr Cys Gly 915 - # 920 - # 925 - - AAA TAC CTC TTC AAC TGG GCA GTA AAA ACC AA - #A CTT AAA CTC ACT CCA 2832 Lys Tyr Leu Phe Asn Trp Ala Val Lys Thr Ly - #s Leu Lys Leu Thr Pro 930 - # 935 - # 940 - - ATC CCG GCT GCG TCC CGG CTG GAC TTG TCC GG - #C TGG TTC GTT GCT GGT 2880 Ile Pro Ala Ala Ser Arg Leu Asp Leu Ser Gl - #y Trp Phe Val Ala Gly 945 9 - #50 9 - #55 9 -#60 - - TAC AGC GGG GGA GAC ATA TAT CAC AGC CTG TC - #T CGT GCC CGA CCCCGT 2928 Tyr Ser Gly Gly Asp Ile Tyr His Ser Leu Se - #r Arg Ala Arg Pro Arg 965 - # 970 - # 975 - - TGG TTC ATG CTG TGC CTA CTC CTA CTT TCT GT - #A GGG GTA GGC ATC TAC 2976 Trp Phe Met Leu Cys Leu Leu Leu Leu Ser Va - #l Gly Val Gly Ile Tyr 980 - # 985 - # 990 - - CTG CTC CCC AAC CGA - # - # - # 2991 Leu Leu Pro Asn Arg 995 - - - - (2) INFORMATION FOR SEQ ID NO:50: - - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 997 amino - #acids (B) TYPE: amino acid (D) TOPOLOGY: linear - - (ii) MOLECULE TYPE: protein - - (xi) SEQUENCE DESCRIPTION: SEQ ID NO:50: - - Gly Tyr Lys Gly Val Trp Arg Gly Asp Gly Il - #e Met Gln Thr Thr Cys 1 5 - # 10 - # 15 - - Pro Cys Gly Ala Gln Ile Thr Gly His Val Ly - #s Asn Gly Ser Met Arg 20 - # 25 - # 30 - - Ile Val Gly Pro Lys Thr Cys Ser Asn Thr Tr - #p His Gly Thr Phe Pro 35 - # 40 - # 45 - - Ile Asn Ala Tyr Thr Thr Gly Pro Cys Thr Pr - #o Ser Pro Ala Pro Asn 50 - # 55 - # 60 - - Tyr Ser Arg Ala Leu Trp Arg Val Ala Ala Gl - #u Glu Tyr Val Glu Val 65 - # 70 - # 75 - # 80 - - Thr Arg Val Gly Asp Phe His Tyr Val Thr Gl - #y Met Thr Thr Asp Asn 85 - # 90 - # 95 - - Val Lys Cys Pro Cys Gln Val Pro Ala Pro Gl - #u Phe Phe Ser Glu Val 100 - # 105 - # 110 - - Asp Gly Val Arg Leu His Arg Tyr Ala Pro Al - #a Cys Arg Pro Leu Leu 115 - # 120 - # 125 - - Arg Glu Glu Val Thr Phe Gln Val Gly Leu As - #n Gln Tyr Leu Val Gly 130 - # 135 - # 140 - - Ser Gln Leu Pro Cys Glu Pro Glu Pro Asp Va - #l Ala Val Leu Thr Ser 145 1 - #50 1 - #55 1 -#60 - - Met Leu Thr Asp Pro Ser His Ile Thr Ala Gl - #u Thr Ala Lys ArgArg 165 - # 170 - # 175 - - Leu Ala Arg Gly Ser Pro Pro Ser Leu Ala Se - #r Ser Ser Ala Ser Gln 180 - # 185 - # 190 - - Leu Ser Ala Pro Ser Leu Lys Ala Thr Cys Th - #r Thr His His Val Ser 195 - # 200 - # 205 - - Pro Asp Ala Asp Leu Ile Glu Ala Asn Leu Le - #u Trp Arg Gln Glu Met 210 - # 215 - # 220 - - Gly Gly Asn Ile Thr Arg Val Glu Ser Glu As - #n Lys Val Val Val Leu 225 2 - #30 2 - #35 2 -#40 - - Asp Ser Phe Asp Pro Leu Arg Ala Glu Glu As - #p Glu Arg Glu ValSer 245 - # 250 - # 255 - - Val Pro Ala Glu Ile Leu Arg Lys Ser Lys Ly - #s Phe Pro Ala Ala Met 260 - # 265 - # 270 - - Pro Ile Trp Ala Arg Pro Asp Tyr Asn Pro Pr - #o Leu Leu Glu Ser Trp 275 - # 280 - # 285 - - Lys Asp Pro Asp Tyr Val Pro Pro Val Val Hi - #s Gly Cys Pro Leu Pro 290 - # 295 - # 300 - - Pro Ile Lys Ala Pro Pro Ile Pro Pro Pro Ar - #g Arg Lys Arg Thr Val 305 3 - #10 3 - #15 3 -#20 - - Val Leu Thr Glu Ser Ser Val Ser Ser Ala Le - #u Ala Glu Leu AlaThr 325 - # 330 - # 335 - - Lys Thr Phe Gly Ser Ser Glu Ser Ser Ala Va - #l Asp Ser Gly Thr Ala 340 - # 345 - # 350 - - Thr Ala Leu Pro Asp Gln Ala Ser Asp Asp Gl - #y Asp Lys Gly Ser Asp 355 - # 360 - # 365 - - Val Glu Ser Tyr Ser Ser Met Pro Pro Leu Gl - #u Gly Glu Pro Gly Asp 370 - # 375 - # 380 - - Pro Asp Leu Ser Asp Gly Ser Trp Ser Thr Va - #l Ser Glu Glu Ala Ser 385 3 - #90 3 - #95 4 -#00 - - Glu Asp Val Val Cys Cys Ser Met Ser Tyr Th - #r Trp Thr Gly AlaLeu 405 - # 410 - # 415 - - Ile Thr Pro Cys Ala Ala Glu Glu Ser Lys Le - #u Pro Ile Asn Ala Leu 420 - # 425 - # 430 - - Ser Asn Ser Leu Leu Arg His His Asn Met Va - #l Tyr Ala Thr Thr Ser 435 - # 440 - # 445 - - Arg Ser Ala Gly Leu Arg Gln Lys Lys Val Th - #r Phe Asp Arg Leu Gln 450 - # 455 - # 460 - - Val Leu Asp Asp His Tyr Arg Asp Val Leu Ly - #s Glu Met Lys Ala Lys 465 4 - #70 4 - #75 4 -#80 - - Ala Ser Thr Val Lys Ala Lys Leu Leu Ser Va - #l Glu Glu Ala CysLys 485 - # 490 - # 495 - - Leu Thr Pro Pro His Ser Ala Lys Ser Lys Ph - #e Gly Tyr Gly Ala Lys 500 - # 505 - # 510 - - Asp Val Arg Asn Leu Ser Ser Lys Ala Val As - #n His Ile His Ser Val 515 - # 520 - # 525 - - Trp Lys Asp Leu Leu Glu Asp Thr Val Thr Pr - #o Ile Asp Thr Thr Ile 530 - # 535 - # 540 - - Met Ala Lys Asn Glu Val Phe Cys Val Gln Pr - #o Glu Lys Gly Gly Arg 545 5 - #50 5 - #55 5 -#60 - - Lys Pro Ala Arg Leu Ile Val Phe Pro Asp Le - #u Gly Val Arg ValCys 565 - # 570 - # 575 - - Glu Lys Met Ala Leu Tyr Asp Val Val Ser Th - #r Leu Pro Gln Val Val 580 - # 585 - # 590 - - Met Gly Ser Ser Tyr Gly Phe Gln Tyr Ser Pr - #o Gly Gln Arg Val Glu 595 - # 600 - # 605 - - Phe Leu Val Asn Thr Trp Lys Ser Lys Lys As - #n Pro Met Gly Phe Ser 610 - # 615 - # 620 - - Tyr Asp Thr Arg Cys Phe Asp Ser Thr Val Th - #r Glu Asn Asp Ile Arg 625 6 - #30 6 - #35 6 -#40 - - Val Glu Glu Ser Ile Tyr Gln Cys Cys Asp Le - #u Ala Pro Glu AlaArg 645 - # 650 - # 655 - - Gln Ala Ile Lys Ser Leu Thr Glu Arg Leu Ty - #r Ile Gly Gly Pro Leu 660 - # 665 - # 670 - - Thr Asn Ser Lys Gly Gln Asn Cys Gly Tyr Ar - #g Arg Cys Arg Ala Ser 675 - # 680 - # 685 - - Gly Val Leu Thr Thr Ser Cys Gly Asn Thr Le - #u Thr Cys Tyr Leu Lys 690 - # 695 - # 700 - - Ala Ser Ala Ala Cys Arg Ala Ala Lys Leu Gl - #n Asp Cys Thr Met Leu 705 7 - #10 7 - #15 7 -#20 - - Val Asn Gly Asp Asp Leu Val Val Ile Cys Gl - #u Ser Ala Gly ThrGln 725 - # 730 - # 735 - - Glu Asp Ala Ala Ser Leu Arg Val Phe Thr Gl - #u Ala Met Thr Arg Tyr 740 - # 745 - # 750 - - Ser Ala Pro Pro Gly Asp Pro Pro Gln Pro Gl - #u Tyr Asp Leu Glu Leu 755 - # 760 - # 765 - - Ile Thr Ser Cys Ser Ser Asn Val Ser Val Al - #a His Asp Ala Ser Gly 770 - # 775 - # 780 - - Lys Arg Val Tyr Tyr Leu Thr Arg Asp Pro Th - #r Thr Pro Leu Ala Arg 785 7 - #90 7 - #95 8 -#00 - - Ala Ala Trp Glu Thr Ala Arg His Thr Pro Va - #l Asn Ser Trp LeuGly 805 - # 810 - # 815 - - Asn Ile Ile Met Tyr Ala Pro Thr Leu Trp Al - #a Arg Met Ile Leu Met 820 - # 825 - # 830 - - Thr His Phe Phe Ser Ile Leu Leu Ala Gln Gl - #u Gln Leu Glu Lys Ala 835 - # 840 - # 845 - - Leu Asp Cys Gln Ile Tyr Gly Ala Cys Tyr Se - #r Ile Glu Pro Leu Asp 850 - # 855 - # 860 - - Leu Pro Gln Ile Ile Glu Arg Leu His Gly Le - #u Ser Ala Phe Ser Leu 865 8 - #70 8 - #75 8 -#80 - - His Ser Tyr Ser Pro Gly Glu Ile Asn Arg Va - #l Ala Ser Cys LeuArg 885 - # 890 - # 895 - - Lys Leu Gly Val Pro Pro Leu Arg Val Trp Ar - #g His Arg Ala Arg Ser 900 - # 905 - # 910 - - Val Arg Ala Arg Leu Leu Ser Gln Gly Gly Ar - #g Ala Ala Thr Cys Gly 915 - # 920 - # 925 - - Lys Tyr Leu Phe Asn Trp Ala Val Lys Thr Ly - #s Leu Lys Leu Thr Pro 930 - # 935 - # 940 - - Ile Pro Ala Ala Ser Arg Leu Asp Leu Ser Gl - #y Trp Phe Val Ala Gly 945 9 - #50 9 - #55 9 -#60 - - Tyr Ser Gly Gly Asp Ile Tyr His Ser Leu Se - #r Arg Ala Arg ProArg 965 - # 970 - # 975 - - Trp Phe Met Leu Cys Leu Leu Leu Leu Ser Va - #l Gly Val Gly Ile Tyr 980 - # 985 - # 990 - - Leu Leu Pro Asn Arg 995__________________________________________________________________________

Number	Date	Country
2-167466	Jun 1990	JPX
2-230921	Aug 1990	JPX
2-305605	Nov 1990	JPX

Number	Name	Date
4464474	Coursaget et al.	Aug 1984
4542016	Trepo	Sep 1985
4673634	Seto et al.	Jun 1987
4808519	Hartley et al.	Feb 1989
5350671	Houghton et al.	Sep 1994

Number	Date	Country
0 293 274	Nov 1988	EPX
0 318 216	May 1989	EPX
0 335 135	Oct 1989	EPX
0 363 025	Apr 1990	EPX
0 377 303	Jul 1990	EPX
0 388 232	Sep 1990	EPX
0 398 748	Nov 1990	EPX
0 414 475	Feb 1991	EPX
0 416 725	Mar 1991	EPX
0 419 182	Mar 1991	EPX
WO9000597	Jan 1990	WOX
WO9002206	Mar 1990	WOX
WO9010060	Sep 1990	WOX

	Number	Date	Country
Parent	324977	Oct 1994
Parent	769996	Oct 1991

Non-A, non-B hepatitis virus genomic cDNA and antigen polypeptide

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CPC

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Abstract

Description

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Priority Claims (3)

Parent Case Info

US Referenced Citations (5)

Foreign Referenced Citations (13)

Non-Patent Literature Citations (3)

Divisions (2)

Continuations (1)

Continuation in Parts (1)

Entry
Kato et al., "Molecular cloning of the human hepatitis C virus genome fromapanese patients with non-A, non-B hepatitis", Proc. Natl. Acad. Sci. 87, 9524-9528, 1990.
Pharmacia P-L, Biochemicals Product Reference Guide 1984, Pharmacia P-L Biochemicals, Inc., Piscataway NJ, pp. 54, 58, 60.
Farci et al., "Lack of protective immunity against reinfection with hepatitis C virus", Science,, vol. 258, pp. 135-140, Oct. 1992.